研究者基本情報

• 博士（獣医学）, 北海道大学, 2023年03月

• https://researchmap.jp/nambat

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202401016274194072

• 71013885

• 202401016274194072

• 尿路上皮
• 尿細管間質
• 泌尿器
• 腎臓
• 動物

• ライフサイエンス, 泌尿器科学
• ライフサイエンス, 腎臓内科学
• ライフサイエンス, 形態、構造
• ライフサイエンス, 解剖学
• ライフサイエンス, 動物生命科学
• ライフサイエンス, 獣医学

• 博士課程, 獣医学院

研究活動情報

• 2022年08月, 日本獣医腎泌尿器学会, 優秀発表賞
• 2019年09月, アジア獣医解剖学会, Best Poster Presentation Award
• 2019年09月, 日本獣医解剖学会, 日本獣医学会奨励賞（一般部門）

• Histological changes of conjunctiva-associated lymphoid tissue caused by pneumonia in Holstein young cows
  Keigo Kosenda; Yuki Ishiguro; Yuto Sano; Kazuya Matsuda; Tomochika Sugiura; Takashi Murakami; Ayano Sato; Hiromichi Ohtsuka; Shigeo Fukuda; Yasuhiro Kon; Takashi Namba; Osamu Ichii
  Veterinary and Animal Science, 32, 100618, 100618, Elsevier BV, 2026年06月
  研究論文（学術雑誌）
• Dominance of conjunctiva-associated lymphoid tissue in the feline ocular immune system, with identification of lacrimal duct-associated lymphoid tissue
  Masaya HIRAISHI; Takashi NAMBA; Yuki OTANI; Shunnosuke KIRA; Osamu ICHII
  Journal of Veterinary Medical Science, 88, 1, 82, 89, Japanese Society of Veterinary Science, 2026年
  研究論文（学術雑誌）
• Age- and sex-dependent morphological alterations of rectal mucosa-associated lymphoid tissue in chickens (Gallus gallus domesticus)
  Md. Zahir Uddin Rubel; Takashi Namba; Masaya Hiraishi; Sao Oe; Osamu Ichii
  Poultry Science, 104, 11, 105846, 105846, Elsevier BV, 2025年11月
  研究論文（学術雑誌）
• Multi-laboratory Validation of Join of the Five Dyes Revealing Collagenous Tissue (JFRL) Staining for Bone Histology Across Animal Species and Bone Implant Materials
  Erika Tsuji; Kanako Sumi; Natsuko Tsuzuki; Daisuke Kondoh; Masashi Tsujio; Marina Hosotani; Takashi Namba; Shoichi Wakitani; Osamu Ichii; Ko Nakanishi; Teppei Nakamura
  Microscopy and Microanalysis, 31, 4, Oxford University Press (OUP), 2025年07月15日, ［査読有り］
  研究論文（学術雑誌）, Abstract
  
  Histological staining is essential for understanding bone structure and pathology; however, variations in decalcification agents can compromise reproducibility. We have previously developed a novel osteochondral staining method, Join of the Five dyes Revealing coLlagenous tissue (JFRL) staining, that is independent of the decalcification method. To promote its widespread adoption, this study confirms the robustness of JFRL staining through intra- and inter-laboratory validation. JFRL staining demonstrated consistent patterns across different manufacturers and facilities, with proper dehydration steps being crucial for optimal results. We applied JFRL staining to diverse vertebrate species prepared under various fixation and decalcification conditions to effectively visualize species-specific bone structures, including distinct osteoid and mineralized bone features from fish to large mammals. Furthermore, JFRL staining proved useful in evaluating bone biomaterials within defect models and clearly depicts the complex architecture of bone-healing processes and material integration. The staining qualitatively distinguished osteoid, mineralized bone, hyaline cartilage, and bone cells of different colors across all applications. These findings establish JFRL staining as a robust and versatile method for bone histology. Future studies focusing on quantitative assessment and pathological applications will prove that JFRL staining presents a reliable tool for both basic research and clinical diagnostics of bone disorders.
• Altered morphology of mucosa-associated lymphoid tissues and epithelium in the nasal cavity and lacrimal apparatus in autoimmune disease-prone MRL/MpJ-Faslpr/lpr mice
  Masaya Hiraishi; Takashi Namba; Teppei Nakamura; Md. Zahir Uddin Rubel; Yasuhiro Kon; Osamu Ichii
  Cell and Tissue Research, Springer Science and Business Media LLC, 2025年03月25日, ［査読有り］
  研究論文（学術雑誌）
• Application of chlorous acid water for disinfection of surgical site in dairy cows.
  Osamu Ichii; Teppei Nakamura; Masaya Hiraishi; Takashi Namba; Md Zahir Uddin Rubel; Takuya Umeyama; Megumi Asai
  Frontiers in veterinary science, 12, 1444674, 1444674, 2025年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Disinfection is crucial for preventing surgical site infections. Recently, the effectiveness of sanitizers using chlorous acid (HClO2) under conditions rich in organic matter has been reported, and chlorous acid water (CAW) has been approved as a food additive. This study evaluated the potential of CAW as a new presurgical disinfectant for cattle. The experiments were performed on the paralumbar fossa of cattle in Sapporo during March (winter to spring) and August (summer). Colony-forming units (CFUs) of standard plate count bacteria (SPCB), Enterococcus faecalis (EF), Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus spp. (SP) were analyzed as indicators of bacterial load. SPCB and SP were abundantly detected, exceeding 6 log10 CFU/100 g on clipped hair and 6 log10 CFU/100 cm2 on the skin immediately after clipping, with no significant seasonal differences. The bacterial load on the skin was evaluated at three time points: after clipping, cleansing, and disinfection. Clipping and cleansing with liquid soap were common procedures, following this, either the standard disinfection protocol using 7.5% iodine scrub for 1 min, 10% povidone-iodine for 5 min, and 70% alcohol for 5 min (SPA), or a modified protocol using CAW with contact times of 15, 10, or 5 min (CAW15, CAW10, CAW5) were performed separately. The cleansing procedure significantly reduced the SPCB, EF, and SP on the skin after clipping, and all disinfection methods significantly decreased the SP after cleansing. Draping significantly enhanced the disinfection efficiency of the SPA, CAW10, and CAW5 protocols. The CAW procedure did not alter skin histology in the paralumbar fossa or udder compared to 10% povidone-iodine or 70% alcohol. Our data suggest that the disinfection method using CAW is useful and comparable to routine disinfection methods and might reduce the time required for presurgical disinfection in farm fields.
• Collagen 17A1 in the Urothelium Regulates Epithelial Cell Integrity and Local Immunologic Responses in Obstructive Uropathy.
  Takashi Namba; Osamu Ichii; Ken Natsuga; Teppei Nakamura; Yuki Otani; Yasuhiro Kon
  The American journal of pathology, 194, 8, 1550, 1570, 2024年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Collagen 17A1 (COL17A1), an epidermal hemidesmosome component, is ectopically induced in the urothelium of mouse and human renal pelvis (RP) in parallel with urinary tract-associated lymphoid structure development. Here, COL17A1 was induced in obstructive uropathy-prone ureter of humans and cats. To ascertain its function, murine urinary organs with unilateral ureteral obstruction (UUO) were analyzed during 1 week after surgery. One day after UUO, COL17A1 expression increased in urothelial cells of RP and ureter, and was positively correlated with renal tubulointerstitial lesions. A portion of RP where the smooth muscle layer from the ureter was interrupted was sensitive to urothelium deciduation and COL17A1 induction, showing urine leaked from the RP lumen into the parenchyma. After urine stimulation, cultured immune cells expressed Cxcl2, also up-regulated in CD11b+ cells following COL17A1 stimulation. One day after UUO, CXCL2+ CD11b+ cells infiltrated the urothelium-disrupted area. However, these numbers were significantly lower in Col17a1-deficient mice. COL17A1+ urothelial cells partially co-expressed cytokeratin-14, a progenitor cell marker for urothelium, whereas Col17a1-deficient mice had lower numbers of cytokeratin-14+ cells. Gene Ontology analysis revealed that expression of epithelial- and immune-associated genes was up-regulated and down-regulated, respectively, in the ureter of Col17a1-deficient mice 4 days after UUO. Thus, COL17A1 maintains urothelium integrity by regulating urothelial cell adhesion, proliferation, and differentiation, and activates local immune responses during obstructive uropathy in mammals.
• Systemic autoimmune abnormalities alter the morphology of mucosa-associated lymphoid tissues in the rectum of MRL/MpJ-Faslpr/lpr mice.
  Md Zahir Uddin Rubel; Osamu Ichii; Takashi Namba; Md Abdul Masum; Tsolmon Chuluunbaatar; Masaya Hiraishi; Teppei Nakamura; Yasuhiro Kon
  Experimental animals, 73, 3, 270, 285, 2024年07月09日, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Systemic autoimmune diseases (ADs) might affect the morphology and function of gut-associated lymphoid tissue (LTs) indirectly; however, their exact relationship remains unclear. Therefore, we investigated mouse LTs in the anorectal canal and morphologically compared them between MRL/MpJ-Fas+/+ and MRL/MpJ-Faslpr/lpr mice. LT aggregations, also known as rectal mucosa-associated lymphoid tissues (RMALTs), were exclusively seen in the lamina propria and submucosa of the rectum. The mean size and number of the LT aggregations both significantly increased in MRL/MpJ-Faslpr/lpr mice compared to those in MRL/MpJ-Fas+/+ mice. The distance from the anorectal junction to the first LT aggregate was significantly shorter in MRL/MpJ-Faslpr/lpr mice than that in MRL/MpJ-Fas+/+ mice. Immunostaining revealed that the RMALTs included CD3+, CD4+, and CD8+ T cells; B220+ B cells; IBA1+ macrophages; Ki67+ proliferative cells; and PNAd+ high-endothelial venules (HEVs). The numbers of macrophages, proliferative cells, CD4+ T cells, CD8+ T cells, and HEVs were significantly increased in MRL/MpJ-Faslpr/lpr mice compared to those in MRL/MpJ mice. Furthermore, the gene expression levels of chemokines (Cxcl9 and Cxcl13) and their corresponding receptors (Cxcr3 and Cxcr5) were significantly higher in MRL/MpJ-Faslpr/lpr mice than those in MRL/MpJ-Fas+/+ mice. Although the morphology of rectal epithelium was comparable between the strains, M cell number was significantly higher in MRL/MpJ-Faslpr/lpr mice than in MRL/MpJ-Fas+/+ mice. Thus, ADs could alter RMALT morphology, and quantitative changes in T-cell subsets, proliferative cells, macrophages, HEVs, chemokine expression, and M cells could affect their cell composition and development.
• Phenotypes of streptozotocin-induced gestational diabetes mellitus in mice.
  Narumi Takahashi; Osamu Ichii; Masaya Hiraishi; Takashi Namba; Yuki Otani; Teppei Nakamura; Yasuhiro Kon
  PloS one, 19, 4, e0302041, 2024年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.
• Species-specific histological characterizations of renal tubules and collecting ducts in the kidneys of cats and dogs.
  Shunnosuke Kira; Takashi Namba; Masaya Hiraishi; Teppei Nakamura; Yuki Otani; Yasuhiro Kon; Osamu Ichii
  PloS one, 19, 7, e0306479, 2024年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The histomorphological features of normal kidneys in cats and dogs have been revealed despite the high susceptibility of cats to tubulointerstitial damage. Herein, the histological characteristics of the two species were compared. Cytoplasmic lipid droplets (LDs) were abundant in the proximal convoluted tubules (PCTs) of cats aged 23-27 months but scarce in dogs aged 24-27 months. LDs were rarely observed in the distal tubules (DTs) and collecting ducts (CDs) of either species, as visualized by the expression of Tamm-Horsfall protein 1, calbindin-D28K, and aquaporin 2. The occupational area ratio of proximal tubules (PTs) in the renal cortex was higher, but that of DTs or CDs was significantly lower in adult cats than in dogs. Single PT epithelial cells were larger, but PCT, DT, and CD lumens were significantly narrower in adult cats than in dogs. Unlike adults, young cats at 6 months exhibited significantly abundant cytoplasmic LDs in proximal straight tubules, indicating lipid metabolism-related development. Histochemistry of the 21 lectins also revealed variations in glycosylation across different renal tubules and CDs in both species. Sodium-glucose cotransporter 2 was expressed only in PTs, excluding the proximal straight tubules with few LDs in adult cats or the PCTs of young cats and adult dogs. These findings are crucial for understanding species-specific characteristics of renal histomorphology and pathogenesis.
• Structural Features of Connective Tissue Formed around Resin Implants Subcutaneously Embedded in Dairy Cows.
  Yuka Katayama; Osamu Ichii; Teppei Nakamura; Keita Yanase; Masaya Hiraishi; Takashi Namba; Yuki Otani; Teppei Ikeda; Erika Tsuji; Natsuko Tsuzuki; Ken Kobayashi; Yasuhiro Kon; Takanori Nishimura
  Animals : an open access journal from MDPI, 13, 23, 2023年11月29日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Foreign body reactions (FBRs) are inadvertently observed in invading or artificially embedded materials, triggering inflammation and subsequent fibrotic processes to occur in situ. Here, we assessed the spatiotemporal formation of connective tissue around implanted materials to establish a technique using connective tissue formed by FBRs as xenografts. An acrylic resin implant, comprising a columnar inner rod and a tubular outer cylinder (OC) with several slits, was embedded in adult dairy cows. Tissues formed in the inner rod and OC groups were histologically analyzed at weeks 2, 4, 8, and 12. Edematous tissues with non-collagenous fibers formed for 2 weeks and showed increased cellularity after 4 weeks. The weight, thickness, amounts of total protein, collagen, DNA, and quantitative scores of α-smooth muscle actin-positive myofibroblasts or elastic fibers notably increased after 8 weeks, with condensed collagen fibers showing orientation. Inflammatory cells were primarily localized in tissues close to the OC, and their numbers increased, with the count of CD204+ cells peaking at 8 weeks and declining at 12 weeks. The count of Ki67+ proliferating cells slightly increased in tissues close to the OC; however, the number and lumen of CD31+ vessels increased. These results may help understand FBR-related tissue remodeling.
• Effects of autoimmune abnormalities on skeletal muscle regeneration after needle puncture in mice.
  Misato Masugi; Osamu Ichii; Yuki Otani; Takashi Namba; Yasuhiro Kon
  Experimental biology and medicine (Maywood, N.J.), 248, 20, 1829, 1840, 2023年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Regeneration of injured skeletal muscles is supported by the activation of satellite cells, and excessive traumatic injuries may trigger abnormal processes, such as fibrosis. Because the participation of immune cells is crucial during skeletal muscle repair, systemic autoimmune diseases impair their regeneration. This study focused on a traumatic injury by injection and investigated the effect of autoimmune diseases on skeletal muscle regeneration. Male mice of MRL/MpJ-Faslpr/lpr and MRL/MpJ (6-7 months old) were used for autoimmune disease and healthy groups. The abdominal walls punctured by a needle were histologically analyzed at 1, 3, and 8 days postinjection. In both groups, injured skeletal muscle tissues showed necrosis and inflammatory cell infiltrations on day 1, increased cell density at 3 days, and regenerative myotubes with central nuclei without fibrosis at 8 days. Gr-1+ neutrophils at injured skeletal muscle were abundant at 1 day, and then substantially decreased starting from 3 days in both groups. The number of CD3+ T cells was remarkably higher in MRL/MpJ-Faslpr/lpr than that in MRL/MpJ at 1 day, and a similar tendency was observed in B220+ B cells. The numbers of IBA1+ macrophages and bromodeoxyuridine-incorporating cells tended to be higher at 3 days, and those of the latter, mainly proliferating paired-box-7+ satellite cells, showed significance at other time points and negatively correlated with the autoimmune disease indices, such as spleen weights or serum autoantibody level. Thus, this result suggested that injured skeletal muscle by minor trauma is normally regenerated regardless of the effects of autoimmune diseases, although lymphocyte infiltrations during these processes were more severe in MRL/MpJ-Faslpr/lpr.
• Analysis of gene expression in poultry red mite, Dermanyssus gallinae, by RNAscope in situ hybridization.
  Hikari Seo; Shiro Murata; Osamu Ichii; Takashi Namba; Shwe Yee Win; Takumi Sato; Eiji Oishi; Akira Taneno; Naoya Maekawa; Tomohiro Okagawa; Satoru Konnai; Kazuhiko Ohashi
  The Journal of veterinary medical science, 85, 5, 532, 535, 2023年05月03日, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, The poultry red mite (PRM; Dermanyssus gallinae) is a hematophagous ectoparasite that mainly infests chickens, and its infestation causes significant economic losses to the poultry industry. In this study, we examined the use of RNAscope-based in situ hybridization (ISH) to characterize gene expression in PRM. We analyzed the mRNA expression of Dermanyssus gallinae cathepsin D-1 (Dg-CatD-1) and Dermanyssus gallinae cystatin (Dg-Cys). RNAscope ISH analysis revealed that mRNA expression of Dg-CatD-1 was observed in the digestive tract, and Dg-Cystatin mRNA was expressed in the ovaries in addition to the digestive tract. RNAscope ISH could be applicable for the analysis of gene expression in each tissue of PRM and is an effective method to investigate the characteristics of target genes.
• Ameliorated Renal Pathological Feature in MRL/MpJ-Faslpr/lpr Background Interleukin-36 Receptor-Deficient Mice.
  Takashi Namba; Osamu Ichii; Tadashi Okamura; Kenta Nakano; Teppei Nakamura; Yuki Otani; Yasuhiro Kon
  Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 29, 2, 675, 685, 2023年04月05日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Systemic autoimmune diseases frequently induce lupus nephritis, causing altered balance and expression of interleukin 36 receptor (IL-36R) ligands, including agonists (IL-36α, β, γ) and antagonists (IL-36Ra, IL-38), in kidneys. Here, we established and analyzed a mouse model of lupus nephritis, MRL/MpJ-Faslpr/lpr with IL-36R-knockout (KO), compared to wild-type (WT) mice. In both genotypes, indices for immune abnormalities and renal functions were comparable, although female WT mice showed higher serum autoantibody levels than males. IL-36R ligand expression did not differ significantly between genotypes at the mRNA level or in IL-36α and IL-38 scores. However, glomerular lesions, especially mesangial matrix expansion, were significantly ameliorated in both sexes of IL-36R-KO mice compared to WT mice. Cell infiltration into the tubulointerstitium with the development of tertiary lymphoid structures was comparable between genotypes. However, the positive correlation with the IL-36α score in WT mice was not evident in IL-36R-KO mice. Fibrosis was less in female IL-36R-KO mice than in WT mice. Importantly, some IL-36α+ nuclei co-localized with acetylated lysine and GCN5 histone acetyltransferase, in both genotypes. Therefore, IL-36R ligands, especially IL-36α, contribute to the progression of renal pathology in lupus nephritis via IL-36R-dependent and IL-36R-independent pathways.
• Expression of Indian hedgehog signaling in murine oviductal infundibulum and its relationship with epithelial homeostasis.
  Marina Hosotani; Osamu Ichii; Takashi Namba; Md Abdul Masum; Teppei Nakamura; Yasuhiro Hasegawa; Takafumi Watanabe; Yasuhiro Kon
  Cell and tissue research, 391, 3, 595, 609, 2023年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Homeostasis of the oviductal infundibulum epithelium is continuously regulated by signaling pathways under physiological and pathological conditions. Herein, we investigated the expression of hedgehog (Hh) signaling-related components in the murine oviductal infundibulum, which is known to maintain homeostasis in the adult epithelium. Additionally, using autoimmune disease-prone MRL/MpJ-Faslpr/lpr (MRL/lpr) mice showing abnormal morphofunction of the ciliated epithelium of the infundibulum related to the oviductal inflammation, we examined the relationship between Hh signaling and pathology of the infundibulum. The expression and localization of Pax8, a marker for progenitor cells in the oviductal epithelium, and Foxj1, a marker for ciliogenesis, were examined in the infundibulum. The results showed that Pax8 was downregulated and Foxj1 was upregulated with aging, suggesting that homeostasis of the infundibulum epithelium of MRL/lpr mice was disturbed at 6 months of age. In all mice, the motile cilia of ciliated epithelial cells in the infundibulum harbored Hh signaling pathway-related molecules: patched (Ptch), smoothened (Smo), and epithelial cells harbor Gli. In contrast, Ptch, Smo, and Gli2 were significantly downregulated in the infundibulum of MRL/lpr mice at 6 months of age. The expression levels of Pax8 and Foxj1 were significantly positively correlated with those of Ptch1, Smo, and Gli2. Hh signaling is thought to be involved in homeostasis of the ciliated epithelium in the infundibulum. In MRL/lpr mice, which show exacerbated severe systemic autoimmune abnormalities, molecular alterations in Hh signaling-related components are considered to interact with local inflammation in the infundibulum, leading to disturbances in epithelial homeostasis and reproductive function.
• Morphological Characteristics of Genital Organ-Associated Lymphoid Tissue in the Vaginal Vestibule of Goats and Pigs.
  Tsolmon Chuluunbaatar; Osamu Ichii; Md Abdul Masum; Takashi Namba; Yasuhiro Kon
  Veterinary sciences, 10, 1, 2023年01月11日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Mucosa-associated lymphoid tissue (MALT) is a specialized form of peripheral lymphoid tissue (LT), which is found on mucosal surfaces exposed to the environment. However, morphological data of these tissues in farm animals are scarce. This study investigated the gross anatomical and histological features of genital organ-associated lymphoid tissues (GOALTs) in the vaginal vestibule (VV) of healthy, non-pregnant, adult goats and pigs. Their VVs were composed of stratified squamous, non-keratinized epithelium, and various-sized dark-blue hematoxylin-positive spots were observed in whole-mount specimens, which were diffusely distributed throughout the mucosal surfaces. These spots were histologically identified as LTs and consisted of lymphatic nodules (LNs) or diffuse lymphoid tissue (DLTs). Both LNs and DLTs contained B cells, T cells, macrophages, dendritic cells, plasma cells, and high endothelial venules. Only the numbers of B cells were significantly higher in both the LNs and DLTs of pigs compared to goats. Furthermore, the surface of the VV epithelium covering the LTs was partially disrupted with a large intercellular space containing abundant connective tissue fibers with numerous lymphocytes. In conclusion, GOALTs in the VV appear to be common local immunological barriers in both examined animals. This knowledge is crucial for understanding the structures and disorders of female reproductive organs in farm animals.
• Transcriptome and proteome analysis of dogs with precursor targeted immune-mediated anemia treated with splenectomy.
  Mei Sugawara-Suda; Keitaro Morishita; Osamu Ichii; Takashi Namba; Keisuke Aoshima; Yumiko Kagawa; Sangho Kim; Kenji Hosoya; Nozomu Yokoyama; Noboru Sasaki; Kensuke Nakamura; Jumpei Yamazaki; Mitsuyoshi Takiguchi
  PloS one, 18, 5, e0285415, 2023年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Precursor-targeted immune-mediated anemia (PIMA) in dogs is characterized by persistent non-regenerative anemia and ineffective erythropoiesis, and it is suspected to be an immune-mediated disease. Most affected dogs respond to immunosuppressive therapies; however, some are resistant. In this study, we carried out splenectomy as an alternative therapy for refractory PIMA in dogs, and analyzed gene expression levels in the spleen of dogs with or without PIMA and in serum before and after splenectomy. A total of 1,385 genes were found to express differentially in the spleens from dogs with PIMA compared with healthy dogs by transcriptome analysis, of which 707 genes were up-regulated, including S100A12, S100A8, and S100A9 that are linked directly to the innate immune system and have been characterized as endogenous damage-associated molecular patterns. Furthermore, immunohistochemistry confirmed that S100A8/A9 protein expression levels were significantly higher in dogs with PIMA compared with those in healthy dogs. A total of 22 proteins were found to express differentially between the serum samples collected before and after splenectomy by proteome analysis, of which 12 proteins were up-regulated in the samples before. The lectin pathway of complement activation was identified by pathway analysis in pre-splenectomy samples. We speculated that S100A8/9 expression may be increased in the spleen of dogs with PIMA, resulting in activation of the lectin pathway before splenectomy. These findings further our understanding of the pathology and mechanisms of splenectomy for PIMA.
• Ureteral morphology and pathology during urolithiasis in cats.
  Osamu Ichii; Kazuhisa Oyamada; Hazuki Mizukawa; Nozomu Yokoyama; Takashi Namba; Yuki Otani; Yaser Hosny Ali Elewa; Noboru Sasaki; Teppei Nakamura; Yasuhiro Kon
  Research in veterinary science, 151, 10, 20, 2022年12月10日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Cats exhibit high susceptibility to urinary organ-related diseases. We investigated the healthy ureter morphologies and compared these with ureters that were surgically resected distal to a urolithiasis obstruction in cats. Healthy ureters (total length 9.88 ± 0.38 cm) developed adventitia composed of collagen fibers (ADCF), containing a longitudinal muscular layer, toward the distal segment. The healthy ureter was the smallest in the middle segment (4.71-6.90 cm from the urinary bladder) with significantly decreased luminal and submucosal areas compared to those in the proximal segment. Diseased cats exhibited a high incidence of calcium oxalate urolithiasis with renal dysfunction, regardless of age, sex, and body size. Diseased ureters showed increased perimeters, inflammation, and decreased nerves in ADCF. Collagen fibers were increased in the submucosal area, intermuscular spaces, and ADCF, particularly near the obstructed lesion. The mean resected ureter length was 5.66 ± 0.49 cm, suggesting a high obstruction risk in the middle segment. The middle segment also increased the cross-sectional area of the ureter and ADCF, regardless of the distance from the obstructed lesion. The ureters in several cases either lacked the transitional epithelium, or exhibited transitional epithelial hyperplasia, and some of these formed the mucosal folds. In conclusion, we demonstrated the following characteristics and histopathological features of cat ureters: decreases in the ureter size, lumen area, and submucosa area from proximal to middle segment in healthy; ADCF changes in urolithiasis, including increased connective tissues with inflammation and decreased nerves. These data are important to understand the pathogenesis of feline ureteral obstruction.
• Modified foreign body reaction to silicone imbedded in subcutaneous tissues by different mouse systemic immune conditions.
  Tomohiro Yamakawa; Osamu Ichii; Teppei Nakamura; Takashi Namba; Yaser Hosny Ali Elewa; Md Abdul Masum; Yuki Otani; Takanori Nishimura; Yasuhiro Kon
  Journal of biomedical materials research. Part A, 110, 12, 1921, 1931, 2022年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Foreign body reaction (FBR) causes unexpected adverse effects due to implanted materials in humans and animals. Inflammation and subsequent fibrosis during FBR seems to be affected by recipient immunity, such as the balance of T helper (Th) response that has the potential to regulate FBR-related macrophage function. Here, the immunological effects of FBR on subcutaneously imbedded silicone tubes (ST) at 8 weeks were investigated histologically by comparing Th1-biased C57BL/6N, Th2-biased MRL/MpJ, and autoimmune disease-prone MRL/MpJ-Faslpr/lpr . Tissue surrounding ST (TSS) was analyzed at day (D) 7 and 14 (reaction phase) or D35 (stability phase) after surgery. In all strains, the TSS was composed of a thin layer (TL) containing fibrous tissues and loose connective tissues formed outside the TL. Few lymphocytes and mast cells, several neutrophils, and numerous macrophages infiltrated the TSS. Active vascularization was observed at D14 in all strains. For the examined indices, M1-type macrophage density in the TSS of C57BL/6N mice was significantly higher at D14 compared to other strains. No significant strain difference relating to M2-type macrophages was detected, suggesting the effects of Th1-biased immunity on FBR-related inflammation. Collagen fibers in the TSS increased in density and became stable with age in all strains. In particular, MRL/MpJ-Faslpr/lpr showed progressive fibrotic features. Serum autoantibody levels in MRL/MpJ-Faslpr/lpr mice were inversely correlated with M1-type macrophage density. These data from MRL/MpJ-Faslpr/lpr mice suggested modifications of FBR-related inflammation and fibrosis by autoimmune abnormalities. The results provide crucial insights into the pathological modification of FBR by recipient immunity and emphasize its clinicopathological importance in humans and animals.
• Genital organ-associated lymphoid tissues arranged in a ring in the mucosa of cow vaginal vestibules.
  Tsolmon Chuluunbaatar; Osamu Ichii; Md Abdul Masum; Takashi Namba; Md Rashedul Islam; Yuki Otani; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Research in veterinary science, 145, 147, 158, 2022年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Female reproductive tracts are equipped with local and mucosal immune systems; however, structural information remains unclear for farm animals. In this study, the mucosa-associated lymphoid tissue-like structures in cow reproductive tracts were described. Vaginal vestibule (VV) and external parts of the genital organ, including the clitoris and vulva, were morphologically analyzed. Whole-mount specimens revealed several hematoxylin-positive spots arranged in a ring in the mucosa. Histologically, these spots were aggregated immune cells and defined as genital organ-associated lymphoid tissues (GOALTs). GOALTs were composed of lymphatic follicles (LFs) or diffuse lymphoid tissues (DLTs) at different depths of lamina propria. LFs frequently contained germinal centers. Scattered lymphocytes occupied the border area between follicles and epithelium, whereas DLTs had indefinite shapes. GOALTs contained immune cells and high endothelial venules. B cells were dominant both in LFs and DLTs. Abundant collagenous fibers were stretched across VV lamina propria, whereas reticular fibers were primarily observed in the DLT rather than LF. The epithelium covering of GOALTs was partially or fully disrupted by the invasion of immune cells toward the VV lumen. These findings suggest GOALTs function as a "genital lymphoid ring" as in Waldeyer's pharyngeal ring and act as immunological gate systems in cow reproductive tracts.
• Close Association between Altered Urine-Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis.
  Osamu Ichii; Marina Hosotani; Md Abdul Masum; Taro Horino; Yuki Otani; Takashi Namba; Teppei Nakamura; Elewa Yaser Hosny Ali; Yasuhiro Kon
  Journal of the American Society of Nephrology : JASN, 33, 1, 88, 107, 2022年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Kidneys with chronic inflammation develop tertiary lymphoid structures (TLSs). Infectious pyelonephritis is characterized by renal pelvis (RP) inflammation. However, the pathologic features of TLSs, including their formation and association with non-infectious nephritis, are unclear. METHODS: RPs from humans and mice that were healthy or had non-infectious chronic nephritis were analyzed for TLS development, and the mechanism of TLS formation investigated using urothelium or lymphoid structure cultures. RESULTS: Regardless of infection, TLSs in the RP, termed urinary tract-associated lymphoid structures (UTALSs), formed in humans and mice with chronic nephritis. Moreover, urine played a unique role in UTALS formation. Specifically, we identified urinary IFN-γ as a candidate factor affecting urothelial barrier integrity because it alters occludin expression. In a nephritis mouse model, urine leaked from the lumen of the RP into the parenchyma. In addition, urine immunologically stimulated UTALS-forming cells via cytokine (IFN-γ, TNF-α) and chemokine (CXCL9, CXCL13) production. CXCL9 and CXCL13 were expressed in UTALS stromal cells and urine stimulation specifically induced CXCL13 in cultured fibroblasts. Characteristically, type XVII collagen (BP180), a candidate autoantigen of bullous pemphigoid, was ectopically localized in the urothelium covering UTALSs and associated with UTALS development by stimulating CXCL9 or IL-22 induction via the TNF-α/FOS/JUN pathway. Notably, UTALS development indices were positively correlated with chronic nephritis development. CONCLUSIONS: TLS formation in the RP is possible and altered urine-urothelium barrier-based UTALS formation may represent a novel mechanism underlying the pathogenesis of chronic nephritis, regardless of urinary tract infection.
• Compartmentalization of interleukin 36 subfamily according to inducible and constitutive expression in the kidneys of a murine autoimmune nephritis model.
  Takashi Namba; Osamu Ichii; Teppei Nakamura; Md Abdul Masum; Yuki Otani; Marina Hosotani; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Cell and tissue research, 386, 1, 59, 77, 2021年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The interleukin (IL) 36 subfamily belongs to the IL-1 family and is comprised of agonists (IL-36α, IL-36β, IL-36γ) and antagonists (IL-36Ra, IL-38). We previously reported IL-36α overexpression in renal tubules of chronic nephritis mice. To understand the localization status and biological relationships among each member of the IL-36 subfamily in the kidneys, MRL/MpJ-Faslpr/lpr mice were investigated as autoimmune nephritis models using pathology-based techniques. MRL/MpJ-Faslpr/lpr mice exhibited disease onset from 3 months and severe nephritis at 6-7 months (early and late stages, respectively). Briefly, IL-36γ and IL-36Ra were constitutively expressed in murine kidneys, while the expression of IL-36α, IL-36β, IL-36Ra, and IL-38 was induced in MRL/MpJ-Faslpr/lpr mice. IL-36α expression was significantly increased and localized to injured tubular epithelial cells (TECs). CD44+-activated parietal epithelial cells (PECs) also exhibited higher IL-36α-positive rates, particularly in males. IL-36β and IL-38 are expressed in interstitial plasma cells. Quantitative indices for IL-36α and IL-38 positively correlated with nephritis severity. Similar to IL-36α, IL-36Ra localized to TECs and PECs at the late stage; however, MRL/MpJ-Faslpr/lpr and healthy MRL/MpJ mice possessed IL-36Ra+ smooth muscle cells in kidney arterial tunica media at both stages. IL-36γ was constitutively expressed in renal sympathetic axons regardless of strain and stage. IL-36 receptor gene was ubiquitously expressed in the kidneys and was induced proportional to disease severity. MRL/MpJ-Faslpr/lpr mice kidneys possessed significantly upregulated IL-36 downstream candidates, including NF-κB- or MAPK-pathway organizing molecules. Thus, the IL-36 subfamily contributes to homeostasis and inflammation in the kidneys, and especially, an IL-36α-dominant imbalance could strongly impact nephritis deterioration.
• Novel polychrome staining distinguishing osteochondral tissue and bone cells in decalcified paraffin sections.
  Teppei Nakamura; Kanako Sumi; Erika Tsuji; Marina Hosotani; Takashi Namba; Osamu Ichii; Takao Irie; Ken-Ichi Nagasaki; Yasuhiro Kon; Takashi Mishima; Tomoji Yoshiyasu
  Cell and tissue research, 385, 3, 727, 737, 2021年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The bone is a dynamic and metabolically active organ in which growth and resorption of the osteochondral matrix is orchestrated by osteoblasts and osteoclasts. For decalcified paraffin-embedded specimens, decalcifying agents alter the staining intensity, and excess decalcification interferes with bone staining. Robust bone staining methods independent of the decalcification conditions and animal species are lacking. In this study, we have developed a novel polychrome staining method, named JFRL staining, which stains the components of osteochondral tissue in different colors. With this staining we could visualize the hyaline cartilage as blue by alcian blue, osteoid as red by picrosirius red, and mineralized bone as green by picro-light green SF or picro-naphthol green B and easily distinguished osteoblasts, osteocytes, and osteoclasts. In mineralized bone, this staining revealed the obvious lamellar structures and woven bone. Notably, this staining was independent of the decalcification conditions and experimental animal species examined. To verify the usefulness of JFRL staining, we observed cotton rat tail which has shorter length and shows a false autotomy. The caudal vertebrae were normally developed via endochondral ossification without a fracture plane. At 6 months of age, the number of chondrocytes declined and the hypertrophic zone was absent at the epiphyseal plate, which might reflect the shorter tail. In conclusion, JFRL staining is the first method to simultaneously distinguish osteochondral matrix and bone cells in one section regardless of decalcifying conditions. This robust staining will provide new information for a wide number of biomedical fields, including bone development, physiology, and pathology.
• Morphological Features of the Testis among Autoimmune Mouse Model and Healthy Strains.
  Zeinab Shouman; Hany E Marei; Ahmed Abd-Elmaksoud; Mohamed Kassab; Takashi Namba; Md Abdul Masum; Yasser Hosny Ali Elewa; Osamu Ichii; Yasuhiro Kon
  Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 1, 9, 2021年08月05日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Autoimmune diseases play a critical role in the progression of infertility in both sexes and their severity has been reported to increase with age. However, few reports have discussed their effect on the morphological features of the testis. Therefore, we compared the morphological alterations in the testes of autoimmune model mice (MRL/MpJ-Faslpr) and the control strain (MRL/MpJ) with those of their background strain (C57BL/6N) at 3 and 6 months. Furthermore, we analyzed the changes in spermatocytes, Sertoli cells, immune cells, and Zonula occludens-1 junctional protein by immunohistochemical staining. The MRL/MpJ-Faslpr mice showed a significant increase in the serum Anti-double stranded DNA antibody level, relative spleen weight, and seminiferous luminal area when compared with other studied two strains. In contrast, a significant decrease in the relative testis weight, and numbers of both Sertoli, meiotic spermatocyte was observed in MRL/MpJ-Faslpr and MRL/MpJ mice compared with C57BL/6N mice especially at 6 months. Similarly, Zonula occludens-1 junctional protein positive cells showed a significant decrease in the same strains at 6 months. However, no immune cell infiltration could be observed among the studied three strains. Our findings suggest that the increase in autoimmune severity especially with age could lead to infertility through loss of spermatogenic and Sertoli cells, rather than the disturbance of the blood-testis barrier.
• Altered Renal Pathology in an Autoimmune Disease Mouse Model After Induction of Diabetes Mellitus.
  Shiori Hiramatsu; Osamu Ichii; Takashi Namba; Yuki Otani; Teppei Nakamura; Md Abdul Masum; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 27, 4, 897, 909, 2021年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Diabetes mellitus (DM) is a predisposing factor for renal disorder progression and is referred to as diabetic kidney disease (DKD). However, there are no reports of DKD with an underlying autoimmune disorder. In this study, we compared the pathophysiological changes caused by DM induction after streptozotocin (STZ) injection in comparison with that in a control group receiving citrate buffer (CB) in the autoimmune disease model mice “BXSB/MpJ-Yaa” (Yaa) and the wild-type strain BXSB/MpJ. Both strains showed hyperglycemia after 12 weeks of STZ injection. Interestingly, the Yaa group developed membranous and proliferative glomerulonephritis, which tended to be milder glomerular lesions in the STZ group than in the CB group, as indicated by a decreased mesangial area and ameliorated albuminuria. Statistically, the indices for hyperglycemia and autoimmune abnormalities were negatively and positively correlated with the histopathological parameters for mesangial matrix production and glomerular proliferative lesions, respectively. STZ treatment induced renal tubular anisonucleosis and dilations in both strains, and they were more severe in Yaa. Significantly decreased cellular infiltration was observed in the Yaa group compared to the CB group. Thus, in DKD related to autoimmune nephritis, hyperglycemia modifies its pathology by decreasing the mesangial area and interstitial inflammation and aggravating renal tubular injury.
• Spatiotemporal histological changes observed in mouse subcutaneous tissues during the foreign body reaction to silicone.
  Sao Oe; Md Abdul Masum; Osamu Ichii; Takanori Nishimura; Teppei Nakamura; Takashi Namba; Yuki Otani; Yasuhide Nakayama; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Journal of biomedical materials research. Part A, 109, 7, 1220, 1231, 2021年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, We investigated spatiotemporal changes in host tissues during foreign body reactions. Silicone tube was subcutaneously embedded into ICR mice, and tissue surrounding silicone (TSS) was observed at 2, 7, 14, 21, 28, 43, and 70 days (D) postsurgery. The thin layer (TL) and loose connective tissues (LCTs) (inside and outside the TSS) developed until D21 and densified afterward. Neutrophils infiltrated the TSS until D14 and formed neutrophil extracellular traps (NETs) in the TL during D7-21. In the LCTs, mast cell counts increased until D21, and macrophage numbers peaked at D14. Several macrophages showed LYVE-1 expression, supporting a tissue-remodeling role. Developmental indices of collagen fibers (CFs) and reticular fibers (RFs) increased during D2-21. NETs, but not neutrophils, were detected after D28. Mast cell numbers peaked at D43 and were maintained until D70. Myofibroblasts consistently localized to the TL from D14. During D21-28, the area of connective tissue (CNT), and CFs and RFs decreased and increased, respectively, and both remained constant during D28-70. The CF density remained constant from D21 and increased at D70. Thus, TSS showed two phases: inflammation and CNT development (D2-21), and inflammation convergence and CNT stabilization (D28-70). These results provide insights into foreign body reactions in clinical cases.
• Comparison of Ovarian Morphology and Follicular Disturbances between Two Inbred Strains of Cotton Rats (Sigmodon hispidus).
  Md Rashedul Islam; Osamu Ichii; Teppei Nakamura; Takao Irie; Akio Shinohara; Md Abdul Masum; Yuki Otani; Takashi Namba; Tsolmon Chuluunbaatar; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Animals : an open access journal from MDPI, 11, 6, 2021年06月12日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Most mammalian ovarian follicles contain only a single oocyte having a single nucleus. However, two or more oocytes and nuclei are observed within one follicle and one oocyte, respectively, in several species, including cotton rat (CR, Sigmodon hispidus). The present study compared ovarian histology, focusing on folliculogenesis, between two inbred CR strains, HIS/Hiph and HIS/Mz. At 4 weeks of age, ovarian sections from both the strains were analyzed histologically. Multi-oocyte follicles (MOFs) and double-nucleated oocytes (DNOs) were observed in all stages of developing follicles in HIS/Hiph, whereas HIS/Mz had MOFs up to secondary stages and lacked DNOs. The estimated total follicles in HIS/Mz were almost half that of HIS/Hiph, but interstitial cells were well developed in HIS/Mz. Furthermore, immunostaining revealed no clear strain differences in the appearance of oocytes positive for Ki67, PCNA, and p63 in MOF or DNOs; no cell death was observed in these oocytes. Ultrastructural analysis revealed more abundant mitochondrial clouds in oocytes of HIS/Hiph than HIS/Mz. Thus, we clarified the strain differences in the CR ovary. These findings indicate that early events during folliculogenesis affect the unique ovarian phenotypes found in CRs, including MOFs or DNOs, and their strain differences.
• Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype.
  Yuki Otani; Osamu Ichii; Md Abdul Masum; Takashi Namba; Teppei Nakamura; Yasuhiro Kon
  Experimental biology and medicine (Maywood, N.J.), 246, 11, 1318, 1329, 2021年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Sex hormones help in maintaining proper immunity as well as renal homeostasis in mammals, and these multi-functional properties characterize the onset of sex-dependent diseases. To clarify the contribution of sex hormones to autoimmune disease-related renal pathogenesis, BXSB/MpJ-Yaa was investigated as a murine autoimmune glomerulonephritis model. BXSB/MpJ-Yaa and its wild-type, BXSB/MpJ-Yaa+ were castrated or sham-operated at three weeks and examined until six months of age. Both castrated strains showed significantly lower serum testosterone levels and body weights than sham-operated mice. Castration did not change the disease phenotypes in BXSB/MpJ-Yaa+. At three months, both sham-operated and castrated BXSB/MpJ-Yaa manifested splenomegaly, autoantibody production, and glomerulonephritis, and castrated BXSB/MpJ-Yaa tended to show heavier spleen weights than the sham-operated group. At six months, both the treated BXSB/MpJ-Yaa showed equivalent autoimmune disease conditions; however, castrated mice clearly showed milder glomerular sclerotic lesions than the sham-operated groups. Urinary albumin excretion in castrated BXSB/MpJ-Yaa was significantly milder than in sham-operated mice at four months, but those of both the treated BXSB/MpJ-Yaa were comparable at six months. The examined renal histopathological indices in parietal epithelial cells were remarkably altered by castration. Briefly, castration decreased the height of parietal epithelial cells and total parietal epithelial cell number in BXSB/MpJ-Yaa at six months. For immunostaining, parietal epithelial cells facing the injured glomeruli of BXSB/MpJ-Yaa expressed CD44, an activated parietal epithelial cell marker, and CD44-positive parietal epithelial cells showed nuclear localization of the androgen receptor and proliferation marker Ki67. CD44- or Ki67-positive parietal epithelial cells were significantly fewer in castrated group than in sham-operated BXSB/MpJ-Yaa at six months. Further, quantitative indices for CD44-positive parietal epithelial cell number and frequency in renal corpuscles positively correlated with glomerular sclerotic severity in BXSB/MpJ-Yaa. In conclusion, androgen seemed to have an effect on both systemic immunity and renal morpho-function; however, the effect on the latter could be more clearly observed in BXSB/MpJ-Yaa, as parietal epithelial cell activation resulted in glomerular sclerosis.
• Anatomy and histology of the foramen of ovarian bursa opening to the peritoneal cavity and its changes in autoimmune disease-prone mice.
  Marina Hosotani; Osamu Ichii; Teppei Nakamura; Takashi Namba; Md Rashedul Islam; Yaser Hosny Ali Elewa; Takafumi Watanabe; Hiromi Ueda; Yasuhiro Kon
  Journal of anatomy, 238, 1, 73, 85, 2021年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The ovarian bursa is a small peritoneal cavity enclosed by the mesovarium and mesosalpinx, which surrounds the ovaries and oviductal infundibulum in mammals. The ovarian bursa is considered as the structure facilitating the transport of ovulated oocytes into the oviduct. Our previous study revealed reduced oocyte pick-up function in the oviduct of lupus-prone MRL/MpJ-Faslpr/lpr mouse, suggesting the possibility of an escape of ovulated oocytes into the peritoneal cavity, despite the presence of an almost complete ovarian bursa in the mouse. In this study, we revealed anatomical and histological characteristics of the ovarian bursa in C57BL/6 N, MRL/MpJ, and MRL/MpJ-Faslpr/lpr mice. All strains had the foramen of ovarian bursa (FOB), with a size of approximately 0.04 to 0.12 cm2 , surrounded by the ligament of ovarian bursa (LOB), which is part of the mesosalpinx. The LOB was partially lined with the cuboidal mesothelial cells and consisted of a thick smooth muscle layer in all strains. In 6-month-old MRL/MpJ-Faslpr/lpr mice, in which the systemic autoimmune abnormality deteriorated and oocyte pick-up function was impaired, the size of the FOB tended to be larger than that of other strains. Additionally, in MRL/MpJ-Faslpr/lpr mice at 6 months of age, there was infiltration by numerous immune cells in the mesosalpinx suspending the isthmus; however, the LOB prevented severe inflammation and showed deposition of collagen fibers. These results not only indicate that the FOB is a common structure within mice, but also imply the physiological function of the LOB and its role in maintaining the microenvironment around the ovary, as well as regulating healthy reproduction.
• Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease.
  Masaya Hiraishi; Md Abdul Masum; Takashi Namba; Yuki Otani; Yaser Ha Elewa; Osamu Ichii; Yasuhiro Kon
  Experimental biology and medicine (Maywood, N.J.), 245, 12, 999, 1008, 2020年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren's syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.
• Unique Running Pattern and Mucosal Morphology Found in the Colon of Cotton Rats.
  Tsolmon Chuluunbaatar; Osamu Ichii; Teppei Nakamura; Takao Irie; Takashi Namba; Md Rashedul Islam; Yuki Otani; Md Abdul Masum; Yuko Okamatsu-Ogura; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Frontiers in physiology, 11, 587214, 587214, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Cotton rats are one of the experimental rodents used for testing different infectious and non-infectious diseases, including gastrointestinal tract pathology. However, their intestinal morphological characteristics are still poorly understood. Here, we clarified the anatomical and histological characteristics of the cecum and ascending colon (AC) of young (1-3-month old), adult (4-6-month old), and old (10-12-month old) cotton rats. The large intestine (LI) in cotton rats is composed of the cecum, AC, transverse and descending colons, and rectum, and is similar to that of other mammals. The AC begins with a double or triple spiral loop-like flexure (SLLF) and ends with a coupled horseshoe-like flexure (HSLF). A single longitudinal mucosal fold (SLMF) was found at the beginning of the AC along the mesentery line and developed with age. Furthermore, the SLMF contained several lymphatic nodules (LNs), indicating their role in digestive and immunological functions. Small and large protuberant LNs were found in the cecum and SLLF, respectively, whereas thin and flat LNs were observed in the HSLF and transverse colon, respectively. Regarding sex-related differences, adult females had a significantly longer AC with a higher number of SLLFs compared to males. The SLMF length and LN number were also longer and higher, respectively, in adult females compared to adult males. These are crucial findings, indicating the presence of sex-related differences in the morphology of the LI in cotton rats, and ours is the first study to discover a sex difference in the mammalian LI lining. Our study clarified the unique morphology of the LI in cotton rats, which could serve as the principal model for elucidating species-specific digestive tract functions and gastrointestinal disorders.
• Vasculature-Associated Lymphoid Tissue: A Unique Tertiary Lymphoid Tissue Correlates With Renal Lesions in Lupus Nephritis Mouse Model.
  Md Abdul Masum; Osamu Ichii; Yaser Hosny Ali Elewa; Yuki Otani; Takashi Namba; Yasuhiro Kon
  Frontiers in immunology, 11, 595672, 595672, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Lupus nephritis (LN) is a common complication in young patients and the most predominant cause of glomerulonephritis. Infiltrating immune cells and presence of immunocomplexes in the kidney are hallmarks of LN, which is closely associated with renal lesions (RLs). However, their regulatory mechanism in the kidney remains unclear, which is valuable for prevention of RL development. Here, we show the development of vasculature-associated lymphoid tissue (VALT) in LN, which is related to renal inflammatory cytokines, indicating that VALT is a unique tertiary lymphoid tissue. Transcriptomic analysis revealed different chemokines and costimulatory molecules for VALT induction and organization. Vascular and perivascular structures showed lymphoid tissue organization through lymphorganogenic chemokine production. Transcriptional profile and intracellular interaction also demonstrated antigen presentation, lymphocyte activity, clonal expansion, follicular, and germinal center activity in VALT. Importantly, VALT size was correlated with infiltrating immune cells in kidney and RLs, indicating its direct correlation with the development of RLs. In addition, dexamethasone administration reduced VALT size. Therefore, inhibition of VALT formation would be a novel therapeutic strategy against LN.
• Developmental Changes of the Ovary in Neonatal Cotton Rat (Sigmodon hispidus).
  Md Rashedul Islam; Osamu Ichii; Teppei Nakamura; Takao Irie; Md Abdul Masum; Yuki Otani; Takashi Namba; Tsolmon Chuluunbaatar; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Frontiers in physiology, 11, 601927, 601927, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The reproductive characteristics and ovarian development in cotton rats (Sigmodon hispidus, CRs) are unclear, although CRs are commonly used as animal models in biomedical research. We previously reported that young (6-8 weeks) CRs showed multi-oocyte follicles (MOFs) and double nucleated oocytes (DNOs) in different stages of follicles. The developmental changes in neonatal CR ovaries were investigated in the present study and were compared with our findings in previous studies of unique phenotypes, particularly in oocytes. CR ovaries at postnatal days (PND) 0, 4, and 7 were obtained from the Hokkaido Institute of Public Health. Samples were analyzed by light and transmission electron microscopy. The general histology and folliculogenesis in CR ovaries were similar to those in other experimental rodents. However, DNOs were observed in all age categories and were frequently observed in primordial follicles, whereas MOFs started to develop from PND4 with greater frequency in primary follicles. Almost all developing follicles expressed DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 and forkhead box L2, which are representative markers of oocytes and follicular epithelial cells, respectively. Ki-67 staining demonstrated the proliferative activity of granulosa cells, but not of oocytes, in follicles. Moreover, rapid folliculogenesis of CR due to a small number of apoptotic oocytes was suggested, based on results of the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, confirming the formation of DNOs or MOFs. These findings clarify the development of unique phenotypes of neonatal CR ovaries and support it as a useful model to better understand folliculogenesis and oocytogenesis as well as their abnormalities in humans and other animals.
• Altered morpho-functional features of bones in autoimmune disease-prone BXSB/MpJ- Yaa mice.
  Takashi Namba; Osamu Ichii; Teppei Nakamura; Md Abdul Masum; Yuki Otani; Saori Otsuka-Kanazawa; Yaser Hosny Ali Elewa; Yasuhiro Kon
  Experimental biology and medicine (Maywood, N.J.), 244, 5, 333, 343, 2019年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Bone disease, such as osteoporosis and rheumatoid arthritis, increases because of the progression of an aging society. Autoimmune disease are important and predisposing factors for the pathogenesis of the bone disease; however, the pathological mechanism is unclear. We have demonstrated that systemic autoimmune disease in BXSB/MpJ- Yaa is closely associated with the morpho-functional abnormalities of bones including bone marrow and has complicated pathology. The abnormalities are characterized by altered regulations of serum calcium, anemia tendency, and hematopoiesis with increased WBCs and decreased PLs, short length and low mass of long bones, imbalance in the populations of osteoclasts and osteoblasts, and increased expression of candidate genes for causing and/or exacerbating their phenotypes. Therefore, BXSB/MpJ- Yaa serves as a model to elucidate bone phenotypes in systemic autoimmune disease that would be affected by the factors in the bone as well as the other immune and/or mineral metabolism organs both in human and experimental medicine.

• 新規骨軟骨染色法(JFRL染色)の医療機器生物学的安全性試験への応用
  辻 絵里香; 鷲見 嘉奈子; 中村 鉄平; 近藤 大輔; 辻尾 祐志; 細谷 実里奈; 難波 貴志; 脇谷 晶一; 市居 修; 西野 光一郎; 昆 泰寛; 三嶋 隆; 吉安 友二; 勝田 真一, 日本バイオマテリアル学会大会予稿集, 44回, 415, 415, 2022年11月
  日本バイオマテリアル学会, 日本語

• アンドロゲンが自己免疫性腎炎モデルマウス腎形態に与える影響
  大谷祐紀; 大江紗央; 難波貴志; Yared Beyene; 池中良徳; 市居修
  第168回日本獣医学会学術集会, 2025年09月05日, 口頭発表（一般）
• 尿路閉塞モデルマウスの尿路における構造的脆弱部位の同定
  難波貴志; 大谷祐紀; 市居 修
  第168回日本獣医学会学術集会, 2025年09月05日, 口頭発表（一般）
• 連続断面解剖によるネコ涙道周囲リンパ組織の観察
  平石真也; 難波貴志; 大谷祐紀; 吉良俊之介; 市居修
  第168回日本獣医学会学術集会, 2025年09月04日, 口頭発表（一般）
• 17型コラーゲンを欠損したマウス尿管の生後発達における形態異常
  酒々井エイミー; 難波貴志; 吉良俊之助; 大江紗央; 平石真也; 大谷祐紀; 夏賀 健; 市居 修
  第168回日本獣医学会学術集会, 2025年09月03日, 口頭発表（一般）
• TRECK法を用いた尿路上皮傷害マウスにおける尿管組織の病態変化
  大江紗央; 難波貴志; 大谷祐紀; 中野堅太; 岡村匡史; 市居 修
  第168回日本獣医学会学術集会, 2025年09月03日, 口頭発表（一般）
• ネコ尿管閉塞に関連した交感神経系の局所的変化
  大江紗央; 難波貴志; 大谷祐紀; 小山田和央; 青木 大; 市居 修
  第17回日本獣医腎泌尿器学会学術集会, 2025年08月24日, 口頭発表（一般）
• ネコ慢性腎臓病における全身および腎局所のビオチン動態の変化
  吉良俊之介; 難波貴志; 大谷祐紀; 小山田和央; 福島建次郎; 山﨑淳平; 菅原芽伊; 横山 望; 中村健介; 市居 修
  第17回日本獣医腎泌尿器学術集会, 2025年08月24日, 口頭発表（一般）
• 自己免疫疾患モデルマウスの頭部にみられる粘膜関連リンパ組織と骨髄の連絡
  平石真也; 難波貴志; 大谷祐紀; 市居修
  第5回日本獣医解剖アカデミア, 2025年03月27日, 口頭発表（一般）
• 17型コラーゲン欠損マウスにおける尿路閉塞病態の表現型解析
  難波貴志; 平石真也; 大谷祐紀; 夏賀健; 市居修
  第5回日本獣医解剖アカデミア, 2025年03月27日, 口頭発表（一般）
• ネコ十二指腸の胆管・膵管開口部にみられる解剖学的特徴と個体差
  久保田 和基; 大江 紗央; 平石 真也; 難波 貴志; 大谷 祐紀; 市居 修
  第21回日本獣医内科学アカデミー学術大会, 2025年02月16日, 口頭発表（一般）
• Morphological sex-related differences found in the rectal mucosa-associated lymphoid tissues of C57BL/6NCrSlc mice
  Rubel MZU; Namba T.; Masum MA; Hiraishi M.; Kon Y.; Ichii O.
  The 4th Join meeting of Veterinary Science in East Asia, 2024年09月09日, 口頭発表（一般）
• Histological characteristics of rectum mucosa-associated lymphoid tissues in auto immune disease-prone MRL/MpJ-Faslpr/lpr mice
  Rubel MZU; Ichii O.; Namba T.; Masum MA; Kon Y.
  The 11th Sapporo summer symposium for one health (SaSSOH), 2023年09月14日, 口頭発表（一般）
• Immune cells constituting the rectal lymphoid tissues in MRL/MpJ-Faslpr/lpr mice
  Rubel MZU; Ichii O.; Namba T.; Masum MA; Kon Y.
  第166回日本獣医学会学術集会, 2023年09月05日, 口頭発表（一般）
• 薬物誘導型妊娠糖尿病モデルマウスの作出とその病態について
  高橋なるみ; 市居修; 大谷祐紀; 難波貴志; 平石真也; 中村鉄平; 昆泰寛
  第166回日本獣医学会学術集会, 2023年09月05日, 口頭発表（一般）
• 薬物誘導型モデルマウスから考察する妊娠糖尿病と腎臓への影響
  高橋なるみ; 市居修; 大谷祐紀; 難波貴志; 平石真也; 中村鉄平; 昆泰寛
  第15回日本獣医腎泌尿器学会学術集会, 2023年08月27日, 口頭発表（一般）
• ネコの腎臓をみなおす-腎臓病対策に有用な形態学的知見を求めて-
  吉良俊之介; 市居修; 難波貴志; 平石真也; 中村鉄平; 昆泰寛
  第15回日本獣医腎泌尿器学会学術集会, 2023年08月27日, 口頭発表（一般）
• Characteristics of lymphoid structures formed in the chicken ureters
  Md Zahir Uddin Rubel; 市居修; 難波貴志; Md Abdul Masum
  第3回⽇本獣医解剖アカデミア, 2023年04月02日, 口頭発表（一般）
• 全身性自己免疫疾患モデルマウスにみられる頭部リンパ組織の形態変化
  平石真也; 市居修; 中村鉄平; 難波貴志; 昆泰寛
  第3回⽇本獣医解剖アカデミア, 2023年04月01日, 口頭発表（一般）
• Genital organ associated lymphoid tissue characteristics in cow, goat, and pig
  Tsolmon Chuluunbaatar; Osamu Ichii; Takashi Namba; Md. Abdul Masum; Yaser Hosny Ali Elewa; Yasuhiro Kon
  The 8th Congress of Asian Association of Veterinary Anatomists, 2022年10月30日, 口頭発表（一般）
• Pathological role of hedgehog signaling in maintenance of the murine oviductal ciliated epithelium
  Hosotani M.; Ichii O.; Namba T.; Nakamura T.; Hasegawa Y.; Masum MA; Watanabe T.; Ueda H.; Kon Y.
  The 8th Congress of Asian Association of Veterinary Anatomists, 2022年10月30日, 口頭発表（一般）
• Characteristics of lymphoid tissue found in large intestine of chicken
  Rubel MZU; Ichii O.; Namba T.; Masum MA; Kon Y.
  The 8th Congress of Asian Association of Veterinary Anatomists, 2022年10月30日, 口頭発表（一般）
• Elucidation of vasculature-associated lymphoid tissue in caprine kidney
  Masum MA、Ichii O.; Otani Y.; Namba T.; Kon Y.
  The 8th Congress of Asian Association of Veterinary Anatomists, 2022年10月30日, 口頭発表（一般）
• Genital organ associated lymphoid tissue characteristics in cow, goat, and pig vaginal vestibule
  Tsolmon Chuluunbaatar; Osamu Ichii; Takashi Namba; Md. Abdul Masum; Yaser Hosny Ali Elewa; Yasuhiro Kon
  The 8th Congress of Asian Association of Veterinary Anatomists, 2022年10月30日, 口頭発表（一般）
• Lymphoid tissues found in mouse anorectal mucosa and systemic factors affecting their morphology
  Rubel MZU; Ichii O.; Namba T.; Masum MA; Tsolmon C.; Yaser Hosny Ali ELEWA; Yasuhiro KON
  The 10th Sapporo summer symposium for one health (SaSSOH), 2022年09月14日, ポスター発表
• Comparison of genital organ associated lymphoid tissue in vaginal vestibule of goat and pig
  Tsolmon、CHULUUNBAATAR、Osamu; ICHII、Takashi; NAMBA; Md. Abdul、MASUM; Yaser Hosny Ali、ELEWA、Yasuhiro、KON
  The 10th Sapporo summer symposium for one health (SaSSOH), 2022年09月14日, ポスター発表
• The relation between systemic immunity and mucosal immunity of the head in autoimmune disease-prone BXSB/MpJ-Yaa mice
  Masaya HIRAISHI; Osamu ICHII; Teppei NAKAMURA; Yuki OTANI; Takashi NAMBA、Ali Elewa; Yaser Hosny; Yasuhiro KON
  The 10th Sapporo summer symposium for one health (SaSSOH), 2022年09月14日, ポスター発表
• Pathological functions of collagen 17A1 in urothelial cells with obstructive uropathy
  Takashi NAMBA; Osamu ICHII; Ken NATSUGA; Teppei NAKAMURA; Yuki OTANI; Yasuhiro KON
  The 10th Sapporo summer symposium for one health (SaSSOH), 2022年09月14日, 口頭発表（一般）
• 乳用種廃用牛を利用した移植用結合組織体の作製－経時的構成変化の解析－
  片山 由佳; 市居 修; 柳瀬 圭太; 中村 鉄平; 池田 哲平; 難波 貴志; 大谷 祐紀; 昆 泰寛; 西邑 隆徳
  第164回日本獣医学会学術集会, 口頭発表（一般）
  2022年09月07日 - 2022年09月13日
• Interleukin-36受容体を欠損した自己免疫性腎炎モデルマウスの腎表現型解析
  難波貴志; 市居修; 岡村匡史; 中野堅太; 中村鉄平; 大谷祐紀; Masum Md. Abdul; Yaser Hosny Ali Elewa; 昆泰寛
  第164回日本獣医学会学術集会, 口頭発表（一般）
  2022年09月07日 - 2022年09月13日
• 骨軟骨組織に対する新規多重染色法(JFRL染色)の有用性
  中村 鉄平; 鷲見 嘉奈子; 辻 絵里香; 都築 奈津子; 近藤 大輔; 辻尾 祐志; 細谷 実里奈; 難波 貴志; 入江 隆夫; 市居 修; 昆 泰寛; 三嶋 隆
  第164回日本獣医学会学術集会, 口頭発表（一般）
  2022年09月07日 - 2022年09月13日
• 慢性腎炎における尿と腎盤上皮の病態連関
  市居 修; 細谷 実里奈; Md. Abdul Masum; 堀野 太郎; 中村 鉄平; 難波 貴志; 大谷 祐紀; Yaser Hosny Ali Elewa; 昆 泰寛
  第164回日本獣医学会学術集会, 口頭発表（一般）
  2022年09月07日 - 2022年09月13日
• 乳用種廃用牛を利用した移植用結合組織体の作製 －スリット形状が与える影響－
  片山由佳; 市居修; 柳瀬圭太; 中村鉄平; 池田哲平; 難波貴志; 大谷祐紀; 昆泰寛; 西邑隆徳
  第165回日本獣医学会学術集会, 2022年09月07日, 口頭発表（一般）
• Genital organ associated lymphoid tissue comparison in vaginal vestibule of goat and pig
  Tsolmon Chuluunbaatar; 市居修; 難波貴志; Md. Abdul Masum; Yaser Hosny Ali Elewa; 昆泰寛
  第165回日本獣医学会学術集会, 2022年09月07日, 口頭発表（一般）
• Lymphoid tissues found in mouse anorectal mucosa and systemic factors affecting their morphology
  Rubel MZU; Ichii O.; Namba T.; Masum MA; Tsolmon C.; Yaser Hosny Ali ELEWA; Yasuhiro KON
  第165回日本獣医学会学術集会, 2022年09月06日, 口頭発表（一般）
• 尿管閉塞モデルマウスの尿管移行上皮に誘導される17型コラーゲンの発現動態
  難波貴志; 市居修; 中村鉄平; 大谷祐紀; 昆泰寛
  第165回日本獣医学会学術集会, 2022年09月06日, 口頭発表（一般）
• BXSB/MpJ-Yaaマウスの病態からみる全身免疫と頭部粘膜免疫の関連
  平石真也; 市居修; 中村鉄平; 大谷祐紀; 難波貴志; Ali Elewa; Yaser Hosny; 昆泰寛
  第165回日本獣医学会学術集会, 2022年09月06日, 口頭発表（一般）
• 閉塞性尿路疾患において移行上皮細胞が発現する17型コラーゲンの多機能性
  難波貴志; 市居修; 夏賀健; 中村鉄平; 大谷祐紀; 昆泰寛
  第14回日本獣医腎泌尿器学会学術集会, 2022年08月28日, 口頭発表（一般）
• ウシの皮下埋植基材周囲に形成される結合組織体の形態解析
  片山由佳; 市居修; 柳瀬圭太; 中村鉄平; 池田哲平; 難波貴志; 大谷祐紀; 昆泰寛; 西邑隆徳
  第2回獣医解剖アカデミア, 2022年04月02日, 口頭発表（一般）
• Lymphoid tissues found in mouse anorectal mucosa and systemic factors affecting their morphology
  Rubel MZU; Ichii O.; Namba T.; Masum MA; Kon Y.
  第2回獣医解剖アカデミア, 2022年04月02日, 口頭発表（一般）
• 腎盤組織構造の部位差と動物種差 －尿路関連リンパ組織との関連－
  難波貴志; 市居修; 中村鉄平; 大谷祐紀; 昆泰寛
  第2回獣医解剖アカデミア, 2022年04月02日, 口頭発表（一般）
• Altered renal phenotype of murine autoimmune nephritis due to a defect of interleukin 36 receptor
  Takashi NAMBA; Osamu ICHII; Tadashi OKAMURA; Kenta NAKANO; Teppei NAKAMURA; Md. Abdul MASUM; Yuki OTANI; Yaser Hosny Ali ELEWA; Yasuhiro KON
  The 9th Sapporo summer symposium for one health (SaSSOH), 2021年09月15日, ポスター発表
• イヌとネコの腎臓における SGLT2 の発現
  市居 修; 大谷 祐紀; Masum; Md.Abdul; 難波 貴志; Yaser Elewa; 昆 泰寛
  第13回日本獣医腎泌尿器学会学術集会, 2021年08月22日, 口頭発表（一般）
• 加齢の Interleukin 36 受容体欠損マウスで観察される上皮組織の形態異常
  難波貴志; 市居修; 中村鉄平; 大谷祐紀; Masum Md. Abdul; Yaser Hosny Ali Elewa; 昆泰寛
  第1回 ⽇本獣医解剖アカデミア, 2021年03月06日, 口頭発表（一般）
• イヌの外頭蓋底にみられる⾆下神経管と顆管の個体差
  大谷祐紀; 市居 修; 難波貴志; 昆 泰寛
  第1回 ⽇本獣医解剖アカデミア, 2021年03月06日, 口頭発表（一般）
• 北海道大学の獣医解剖学教育における感染症対策－2020 年度－
  市居 修; 難波貴志; 大谷祐紀; Yaser Hosny Ali Elewa; 昆 泰寛
  第1回 ⽇本獣医解剖アカデミア, 2021年03月06日, 口頭発表（一般）
• Elucidation of vasculature-associated tertiary lymphoid tissue in lupus nephritis mouse model
  Md. Abdul Masum; 市居 修; 難波貴志; 大谷祐紀; Yaser Hosny Ali Elewa; 昆 泰寛
  第1回 ⽇本獣医解剖アカデミア, 2021年03月06日, 口頭発表（一般）
• 自己免疫疾患モデルマウスの解析からみる腎臓内IL-36群の機能的棲み分け
  難波 貴志; 市居 修; 中村 鉄平; 大谷 祐紀; Md. Abdul Masum; Yaser Hosny Ali Elewa; 昆 泰寛
  第163回日本獣医学会学術集会, 口頭発表（一般）
  2020年09月14日 - 2020年09月30日
• アンドロゲンは自己免疫性腎炎モデルマウスの糸球体硬化を増悪させる
  大谷 祐紀; 市居 修; Md. Abdul Masum; 難波 貴志; 昆 泰寛
  第163回日本獣医学会学術集会, 口頭発表（一般）
  2020年09月14日 - 2020年09月30日
• 自己免疫疾患モデルマウスを用いた糖尿病性腎臓病の病態解明アプローチ
  平松 栞; 市居 修; 難波 貴志; 大谷 祐紀; Md. Abdul Masum; 中村 鉄平; Yaser Hosny Ali Elewa; 昆 泰寛
  第163回日本獣医学会学術集会, 口頭発表（一般）
  2020年09月14日 - 2020年09月30日
• Enhanced IL-36α expression in the kidneys of autoimmune disease-prone mice
  Takashi NAMBA; Osamu ICHII; Teppei NAKAMURA; Md. Abdul MASUM; Yaser Hosny Ali ELEWA; Yasuhiro KON
  The 8th Sapporo Summer Seminar for One Health (SaSSOH), ポスター発表
  2020年09月16日 - 2020年09月17日
• 自己免疫疾患モデルマウスで変化する腎臓内 Interleukin 1 family の発現バランス
  難波 貴志; 市居 修; 中村 鉄平; Yaser Hosny Ali Elewa; 昆 泰寛
  第162回日本獣医学会学術集会, 2019年09月12日, 口頭発表（一般）
• 自己免疫疾患モデルマウスにみられる涙液産生組織の形態学的変化
  平石 真也; 市居 修; 中村 鉄平; 難波 貴志; Yaser Hosny Ali Elewa; 昆 泰寛
  第162回日本獣医学会学術集会, 2019年09月12日, 口頭発表（一般）
• マウス生体内異物反応の経時観察 ―組織局所の炎症と線維化の関連性―
  大江 紗央; 市居 修; 難波 貴志; 大谷 祐紀; Masum Md. Abdul; 中村 鉄平; Yaser Hosny Ali Elewa; 西邑 隆徳; 中山 泰秀; 昆 泰寛
  第162回日本獣医学会学術集会, 2019年09月12日
• マウスの卵巣嚢－腹腔連絡路（卵巣嚢孔）
  細谷 実里奈; 市居 修; 中村 鉄平; 難波 貴志; Yaser Hosny Ali Elewa; 渡邉 敬文; 植田 弘美; 昆 泰寛
  第162回日本獣医学会学術集会, 2019年09月12日
• Altered bone morpho-function in autoimmune disease-prone mice
  Takashi Namba; Osamu Ichii; Md. Abdul Masum; Yuki Otani; Saori Otsuka-Kanazawa; Yaser Hosny Ali Elewa; Yasuhiro Kon
  The 7th Congress of Asian Association of Veterinary Anatomists (Asian AVA), 2019年09月, ポスター発表
• 自己免疫疾患モデルマウスの骨に観察される形態機能的変化
  難波貴志; 市居 修; Yaser Hosny Ali Elewa; 中村鉄平; 木村純平; 大谷祐紀; Md. Abdul Masum; 昆 泰寛
  第161回日本獣医学会学術集会, 2018年09月11日, 口頭発表（一般）

• 組織学実習, 2024年, 学士課程, 獣医学部

• 2020年08月 - 現在
  日本獣医腎泌尿器学会
• 2018年07月 - 現在
  日本獣医学会

• 腎臓の慢性炎症を導く尿路関連リンパ組織の加齢性発達機序
  科学研究費助成事業
  2025年04月 - 2029年03月
  市居 修; 岡村 匡史; 福島 建次郎; 大谷 祐紀; 山崎 淳平; 中村 鉄平; 堀野 太郎; 難波 貴志
  日本学術振興会, 基盤研究(A), 北海道大学, 25H00957
• ネコの腎臓に出現する巨大ビオチン含有構造物の発見
  科学研究費助成事業
  2025年06月 - 2028年03月
  市居 修; 福島 建次郎; 大谷 祐紀; 山崎 淳平; 難波 貴志
  日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 25K22407
• 泌尿器疾患と17型コラーゲンの病態連関を解き明かす生物種横断的アプローチ
  科学研究費助成事業
  2025年07月31日 - 2027年03月31日
  難波 貴志
  日本学術振興会, 研究活動スタート支援, 北海道大学, 25K23668
• 動物の腎－骨連関を繋ぐIL-36：分子病態の解明から臨床応用へ
  科学研究費助成事業
  2020年04月24日 - 2023年03月31日
  難波 貴志
  ヒトと伴侶動物の高齢化に伴い、両者の慢性腎臓病症例数が増加している。また近年、慢性腎臓病に伴う骨ミネラル代謝異常の対策も重要視されている。本研究では、腎および骨の炎症に関与する免疫、特に炎症性サイトカインであるIL-36群に着目した。これは、作動分子群(IL-36α, β, γ)と拮抗分子群(IL-36Ra, IL-38)からなり、全ての分子はIL-36受容体(IL-36R)に結合し炎症を制御する。そこで、自己免疫性腎炎モデルマウスMRL/MpJ-Faslpr/lpr(lpr)を用いて、IL-36群の発現動態を中心に腎および骨病態を解析した。
  IL-36群の腎臓内局在について、IL-36RaとIL-36γが脈管神経系で恒常的に発現した一方、IL-36αは障害された遠位尿細管や糸球体包外壁に、IL-36βとIL-38は浸潤細胞に発現誘導された。また、IL-36Rは腎臓内で遍在性に局在したが、腎炎進行に伴い障害された腎上皮細胞で発現誘導された。健常ネコ腎組織を用いた解析より、IL-36RのmRNAはマウスIL-36αとIL-36Rの局在と一致した。
  次に、IL-36R欠損lprを用いて、その腎表現型を野生型マウスと比較した。両群間の腎機能指標は同等だった一方、欠損群の糸球体と尿細管間質の病理指標は、野生型と比べ軽度だった。またIL-36Rの有無に関わらず、IL-36αは腎上皮細胞の細胞質と核に局在し、その一部はヒストンアセチル化マーカーと核内で共局在しており、IL-36Rを介さない核内IL-36αシグナルの存在が示唆された。一方、両群間の骨病態に差はなかった。
  以上、腎臓に発現するIL-36群、特にIL-36αの過剰発現は自己免疫性腎炎の病態形成に寄与し、そのIL-36R依存的および非依存的経路が示唆された。また、本分子群を標的とした腎疾患への獣医学的な応用可能性が考えられた。
  日本学術振興会, 特別研究員奨励費, 北海道大学, 20J22559