Researcher Database

Saori Nishio
Hokkaido University Hospital Internal Medicine

Researcher Profile and Settings


  • Hokkaido University Hospital Internal Medicine

Job Title

  • Lecturer

J-Global ID

Research Interests

  • 常染色体優性多発性嚢胞腎   Sec63   常染色体優性遺伝性肝嚢胞   水腎症   常染色体優性多発性肝嚢胞   細胞増殖   cilia   アポトーシス   トランスジェニックメダカ   Pkd1ノックアウトマウス   多発性嚢胞腎   PKD2   PKD1   ADPKD   ADPKD、PKD1、PKD2、PKD1ノックアウトマウス   

Research Areas

  • Life sciences / Nephrology

Academic & Professional Experience

  • 2009 - 2011 Hokkaido University

Research Activities

Published Papers

  • Junya Yamamoto, Saori Nishio, Fumihiko Hattanda, Daigo Nakazawa, Toru Kimura, Michio Sata, Minoru Makita, Yasunobu Ishikawa, Tatsuya Atsumi
    KIDNEY INTERNATIONAL 92 (2) 377 - 387 0085-2538 2017/08 [Refereed][Not invited]
    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1(flox/flox): Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age. The BCAA group showed significantly greater kidney/body weight ratio and higher cystic index in both the kidney and liver compared to the placebo-treated mice. We found that the L-type amino acid transporter 1 that facilitates BCAA entry into cells is strongly expressed in cells lining the cysts. We also found increased cyst-lining cell proliferation and upregulation of mTOR and mitogenactivated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways in the BCAA group. In vitro, we cultured renal epithelial cell lines from Pkd1 null mice with or without leucine. Leucine was found to stimulate cell proliferation, as well as activate mTOR and MAPK/ERK pathways in these cells. Thus, BCAA accelerated disease progression by mTOR and MAPK/ERK pathways. Hence, BCAA may be harmful to patients with ADPKD.
  • Shigeo Horie, Toshio Mochizuki, Satoru Muto, Kazushige Hanaoka, Yoshimitsu Fukushima, Ichiei Narita, Kikuo Nutahara, Ken Tsuchiya, Kazuhiko Tsuruya, Koichi Kamura, Saori Nishio, Tatsuya Suwabe, Yoshifumi Ubara, Eiji Ishimura, Koichi Nakanishi, Keiichi Furukawa, Kenjiro Kimura, Seiichi Matsuo
    CLINICAL AND EXPERIMENTAL NEPHROLOGY 20 (4) 493 - 509 1342-1751 2016/08 [Refereed][Not invited]
  • Horie S, Mochizuki T, Muto S, Hanaoka K, Fukushima Y, Narita I, Nutahara K, Tsuchiya K, Tsuruya K, Kamura K, Nishio S, Suwabe T, Ubara Y, Ishimura E, Nakanishi K, Furukawa K, Kimura K, Matsuo S
    Clinical and experimental nephrology 20 (4) 510  1342-1751 2016/08 [Refereed][Not invited]
  • Daigo Nakazawa, Haruki Shida, Yoshihiro Kusunoki, Arina Miyoshi, Saori Nishio, Utano Tomaru, Tatsuya Atsumi, Akihiro Ishizu
    JOURNAL OF AUTOIMMUNITY 67 19 - 28 0896-8411 2016/02 [Refereed][Not invited]
    Neutrophil extracellular traps (NETs) are net-like chromatin fibers decorated with antimicrobial proteins, which are released from dying neutrophils. The death of neutrophils with NET formation is called NETosis. Although NETs play important roles in the innate immunity, especially in the elimination of microbes, the extracellular release of DNA and intra-cytoplasmic/nuclear proteins can, on the other hand, result in diverse adversities to the hosts. Therefore, NETosis is adequately regulated in vivo. Currently, two mechanisms, namely DNase I-dependent digestion and phagocytosis by macrophages, have been shown as such regulatory mechanisms. In this study, we focused on the interaction of macrophages and neutrophils that underwent NETosis. Results demonstrated that macrophages displayed a phenotype dependent response after degradation of NETs. Several hours after the interaction, M2 macrophages induced a pro-inflammatory response, while M1 macrophages underwent cell death with nuclear decondensation. This nuclear decondensation of M1 macrophages occurred in a peptidylarginine deiminase 4-dependent manner and resulted in a local release of extracellular DNA. Thereafter, M1 macrophages degraded DNA derived from themselves in a caspase-activated DNase-dependent manner resulting in the clearance of extracellular DNA within 24 h. This transient increase and subsequent clearance mechanism of extracellular DNA seems very reasonable in terms of the double-edged sword-like property of NETs. The collective findings demonstrate a novel phenotype- and time-dependent regulation of NETosis by macrophages. (C) 2015 The Authors. Published by Elsevier Ltd.
  • Kusunoki Y, Nakazawa D, Shida H, Hattanda F, Miyoshi A, Masuda S, Nishio S, Tomaru U, Atsumi T, Ishizu A
    Frontiers in immunology 7 227  2016 [Refereed][Not invited]
  • Yusuke Sakuhara, Saori Nishio, Ken Morita, Daisuke Abo, Yu Hasegawa, Noriaki Yuasa, Toshio Mochizuki, Takeshi Soyama, Koji Oba, Hiroki Shirato, Kohsuke Kudo
    Radiology 277 (1) 277 - 85 0033-8419 2015/10 [Refereed][Not invited]
    PURPOSE: To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) with ethanol in symptomatic patients with enlarged polycystic kidney disease. MATERIALS AND METHODS: This prospective study was institutional review board approved and was planned for patients with symptoms related to enlarged polycystic kidney disease, such as a markedly distended abdomen, gastroesophageal reflux, and abdominal pain. At the time of TAE, all patients were undergoing dialysis therapy for chronic renal failure, and their urinary volume had decreased to less than 500 mL per day. Bilateral renal TAE with absolute ethanol was performed, and changes in kidney volume, clinical symptoms, laboratory data, and complications were evaluated after TAE. The differences in patients' kidney volumes, clinical symptoms, abdominal circumference, and dry weights before and after TAE were analyzed with a mixed effect model. RESULTS: Fifteen patients (seven men and eight women; mean age, 57.7 years ± 5.3 [standard deviation]) were treated. Among the 15 patients, the follow-up period was 24 months in 13 patients, 6 months in one patient, and 3 months in one patient. The mean kidney volume was 3380 mL before renal TAE, and at 3, 12, and 24 months after TAE, it significantly decreased to 60.9%, 39.8%, and 32.1% of the pretherapeutic value, respectively (P < .001). All patients reported improved clinical symptoms within 3 months after TAE (P < .001). Abdominal circumferences were significantly decreased after TAE (P < .001). The dry weights also continued to significantly decreased until 6 months after TAE (P < .001), at which point they began to slightly increase until 24 months after TAE. Abdominal pain, nausea, and inflammatory response developed in all patients after TAE, but these symptoms improved with conservative treatment. Abscess formation was found in one kidney, and drainage catheter placement was performed. No major complications related to TAE occurred in the remaining patients. CONCLUSION: Renal contraction therapy by TAE with ethanol injection appears to be a safe and effective treatment in patients with symptomatic enlarged polycystic kidney disease.
  • Hitoshi Yokoyama, Hitoshi Sugiyama, Ichiei Narita, Takao Saito, Kunihiro Yamagata, Saori Nishio, Shouichi Fujimoto, Noriko Mori, Yukio Yuzawa, Seiya Okuda, Shoichi Maruyama, Hiroshi Sato, Yoshihiko Ueda, Hirofumi Makino, Seiichi Matsuo
    CLINICAL AND EXPERIMENTAL NEPHROLOGY 19 (3) 496 - 505 1342-1751 2015/06 [Refereed][Not invited]
    There are very little data available regarding nephrotic syndrome (NS) in elderly (aged a parts per thousand yen65 years) Japanese. The aim of this study was to examine the causes and outcomes of NS in elderly patients who underwent renal biopsies between 2007 and 2010. From July 2007 to June 2010, all of the elderly (aged a parts per thousand yen65 years) Japanese primary NS patients who underwent native renal biopsies and were registered in the Japan renal biopsy registry (J-RBR; 438 patients including 226 males and 212 females) were identified. From this cohort, 61 patients [28 males and 33 females including 29, 19, 6, 4, and 3 patients with membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), and other conditions, respectively] were registered from the representative multi-centers over all districts of Japan, and analyzed retrospectively. The treatment outcome was assessed using proteinuria-based criteria; i.e., complete remission (CR) was defined as urinary protein level of < 0.3 g/day or g/g Cr, and incomplete remission type I (ICR-I) was defined as urinary protein level of < 1.0-0.3 g/day or g/g Cr, and renal dysfunction was defined as a serum creatinine (Cr) level of 1.5 times the baseline level. In this elderly primary NS cohort, MN was the most common histological type of NS (54.8 %), followed by MCNS (19.4 %), FSGS (17.4 %), and MPGN (8.4 %). Of the patients with MN, MCNS, or FSGS, immunosuppressive therapy involving oral prednisolone was performed in 25 MN patients (86.2 %), 18 MCNS patients (94.7 %), and all 6 FSGS patients (100 %). CR was achieved in all 19 (100 %) MCNS patients. In addition, CR and ICR-I were achieved in 16 (55.2 %) and 18 (62.1 %) MN patients and 4 (66.7 %) and 5 (83.3 %) FSGS patients, respectively. There were significant differences in the median time to CR among the MCNS, FSGS, and MN patients (median: 26 vs. 271 vs. 461 days, respectively, p < 0.001), and between the elderly (65-74 years, n = 7) and very elderly (aged a parts per thousand yen75 years, n = 12) MCNS patients (7 vs. 22 days, p = 0.037). Relapse occurred in two (6.9 %) of the MN and nine (47.4 %) of the MCNS patients. Renal dysfunction was observed in five (7.2 %) of the MN patients. Serious complications developed in eight (14.8 %) patients, i.e., two (3.7 %) patients died, four (7.4 %, including three MCNS patients) were hospitalized due to infectious disease, and two (3.7 %) developed malignancies. The initiation of diabetic therapy was necessary in 14 of the 61 patients (23.0 %) with much higher initial steroid dosage. Renal biopsy is a valuable diagnostic tool for elderly Japanese NS patients. In this study, most of elderly primary NS patients respond to immunosuppressive therapy with favorable clinical outcomes. On the other hand, infectious disease is a harmful complication among elderly NS patients, especially those with MCNS. In future, modified clinical guidelines for elderly NS patients should be developed.
  • Masahide Yazaki, Tsuneaki Yoshinaga, Yoshiki Sekijima, Saori Nishio, Yuji Kanizawa, Fuyuki Kametani, Kana Miyashita, Naomi Hachiya, Keiichi Higuchi, Shu-ichi Ikeda
    AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS 22 (2) 142 - 144 1350-6129 2015/06 [Refereed][Not invited]
  • Nishio S
    Nihon Jinzo Gakkai shi 57 (8) 1354 - 1358 0385-2385 2015 [Refereed][Not invited]
  • Takuya Toyonaga, Osamu Manabe, Florian C Gaertner, Tasuku Nakagaki, Saori Nishio, Akira Suzuki, Nagara Tamaki
    Clinical nuclear medicine 39 (7) 648 - 9 0363-9762 2014/07 [Refereed][Not invited]
    We report about the usefulness of F-FDG PET for the detection and therapy response evaluation of renal sarcoidosis. A 55-year-old woman presented with a condition diagnosed with pulmonary and ocular sarcoidosis 2 years before having anemia and acute deterioration of renal function. FDG PET revealed diffuse increased FDG uptake in both kidneys and the spleen. Histopathologic examination of a renal biopsy sample revealed granulomatous interstitial nephritis with sarcoidosis. After methylprednisolone treatment, the abnormal FDG uptake resolved completely with improvement of symptoms. FDG PET is a useful tool to detect active sarcoidosis regions and to monitor treatment efficacy.
  • Daigo Nakazawa, Haruki Shida, Utano Tomaru, Masaharu Yoshida, Saori Nishio, Tatsuya Atsumi, Akihiro Ishizu
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 25 (5) 990 - 997 1046-6673 2014/05 [Refereed][Not invited]
    AKI involves early Toll-like receptor (TLR)-driven immunopathology, and resolution of inflammation is needed for rapid regeneration of injured tubule cells. Notably, activation of TLRs also has been implicated in epithelial repair. We hypothesized that TLR signaling drives tubule regeneration after acute injury through the induction of certain ILs. Systematic screening in vitro identified IL-22 as a candidate proregeneratory factor in primary tubular cell recovery, and IL-22 deficiency or IL-22 blockade impaired post-ischemic tubular recovery after AKI in mice. Interstitial mononuclear cells, such as dendritic cells and macrophages, were the predominant source of IL-22 secretion, whereas IL-22 receptor was expressed by tubular epithelial cells exclusively. Depleting IL-22-producing cells during the healing phase impaired epithelial recovery, which could be rescued entirely by reconstituting mice with IL-22. In vitro, necrotic tubular cells and oxidative stress induced IL-22 secretion selectively through TLR4. Although TLR4 blockade during the early injury phase prevented tubular necrosis and AKI, TLR4 blockade during the healing phase suppressed IL-22 production and impaired kidney regeneration. Taken together, these results suggest that necrotic cell-derived TLR4 agonists activate intrarenal mononuclear cells to secrete IL-22, which accelerates tubular regeneration and recovery in AKI.
  • Nakazawa D, Nishio S, Tomaru U, Atsumi T, Ishizu A
    Nihon Jinzo Gakkai shi 56 (2) 117 - 123 0385-2385 2014 [Refereed][Not invited]
  • Yamamoto J, Nakazawa D, Tsukaguchi H, Toyoyama T, Sato A, Nakagaki T, Ishikawa Y, Shibazaki S, Nishio S, Atsumi T
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 102 (5) 1220 - 1222 0021-5384 2013/05 [Refereed][Not invited]
  • Megumi Oshima, Shinji Kitajima, Tadashi Toyama, Akinori Hara, Kiyoki Kitagawa, Yasunori Iwata, Miho Shimizu, Saori Nishio, Junko Imura, Hitoshi Yokoyama, Kengo Furuichi, Shuichi Kaneko, Takashi Wada
    INTERNAL MEDICINE 52 (14) 1605 - 1609 0918-2918 2013 [Refereed][Not invited]
    We herein report a case of spontaneous pregnancy and preterm delivery in a 29-year-old patient with myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Her basal serum creatinine level before pregnancy was 1.4 mg/dL and her urinary protein level was approximately 2 g/day. The proteinuria and hematuria increased during pregnancy, and the patient was admitted to our hospital and treated with prednisolone (PSL). At 27 weeks of gestation, she delivered a live infant weighing 848 g via cesarean section. No relapse of ANCA-associated glomerulonephritis occurred.
  • Daigo Nakazawa, Utano Tomaru, Akira Suzuki, Sakiko Masuda, Risa Hasegawa, Toshiaki Kobayashi, Saori Nishio, Masanori Kasahara, Akihiro Ishizu
    ARTHRITIS AND RHEUMATISM 64 (11) 3779 - 3787 0004-3591 2012/11 [Refereed][Not invited]
    Objective Neutrophil extracellular traps (NETs) are composed of DNA and antimicrobial proteins, including myeloperoxidase (MPO). Recent studies have demonstrated that impaired regulation of NETs could trigger an autoimmune response. Propylthiouracil (PTU), an antithyroid drug, is associated with a risk of MPO antineutrophil cytoplasmic antibody (ANCA) production and MPO ANCA-associated vasculitis (MPO AAV). This study was undertaken to clarify the mechanism of MPO ANCA production, using the PTU-induced model of MPO AAV. Methods NETs were induced by treating human neutrophils with phorbol myristate acetate (PMA) in vitro. We examined whether the addition of PTU influenced the NET formation induced by PMA and the degradation of NETs by DNase I, which is regarded as a regulator of NETs. Furthermore, we examined whether NETs generated by the combination of PMA and PTU induced MPO ANCA and MPO AAV in vivo in rats. Results When NETs were induced by PMA with PTU using human neutrophils in vitro, abnormal conformation of NETs was observed. Interestingly, the abnormal NETs were hardly digested by DNase I. Moreover, rats immunized with the abnormal NETs, which had been induced by PMA with PTU using rat neutrophils, produced MPO ANCA and developed pulmonary capillaritis. When rats were given oral PTU with intraperitoneal injection of PMA, pauci-immune glomerulonephritis and pulmonary capillaritis occurred with MPO ANCA production in the serum. Conclusion Our findings indicate that abnormal conformation and impaired degradation of NETs induced by PTU are involved in the pathogenesis of PTU-induced MPO ANCA production and MPO AAV. These findings suggest that disordered NETs can be critically implicated in the pathogenesis of MPO AAV.
  • Eiji Higashihara, Shigeo Horie, Satoru Muto, Toshio Mochizuki, Saori Nishio, Kikuo Nutahara
    CLINICAL AND EXPERIMENTAL NEPHROLOGY 16 (4) 622 - 628 1342-1751 2012/08 [Refereed][Not invited]
    Autosomal dominant polycystic kidney disease is a lifelong progressive disorder. However, how age, blood pressure, and stage of chronic kidney disease (CKD) affect the rate of kidney function deterioration is not clearly understood. In this long-term observational case study up to 13.9 years (median observation period for slope was 3.3 years), serum creatinine was serially measured in 255 mostly adult patients. The glomerular filtration rate was estimated (eGFR) using a modified Modification of Diet in Renal Disease Study method. The total kidney volume (TKV) has been measured in 86 patients at one center since 2006. As age increased, eGFR declined significantly (P < 0.0001), but the annual rate of decline of eGFR did not correlate with age or initially measured eGFR. In patients with CKD stage 1, eGFR declined at a rate which was not significantly different from other advanced CKD stages. Hypertensive patients had lower eGFR and larger TKV than normotensive patients at a young adult age. The slopes of regression lines of eGFR and TKV in relation to age were not different between high and normal blood pressure groups. The declining rate of eGFR was relatively constant and did not correlate with age or eGFR after adolescence. eGFR was already low in young adult patients with hypertension. As age increased after adolescence, eGFR declined and TKV increased similarly between normal and high blood pressure groups. eGFR starts to decline in patients with normal eGFR, suggesting that the decline starts earlier than previously thought.
  • Sorin V. Fedeles, Xin Tian, Anna-Rachel Gallagher, Michihiro Mitobe, Saori Nishio, Seung Hun Lee, Yiqiang Cai, Lin Geng, Craig M. Crews, Stefan Somlo
    NATURE GENETICS 43 (7) 639 - U163 1061-4036 2011/07 [Refereed][Not invited]
    Autosomal dominant polycystic liver disease results from mutations in PRKCSH or SEC63. The respective gene products, glucosidase II beta and SEC63p, function in protein translocation and quality control pathways in the endoplasmic reticulum. Here we show that glucosidase II beta and Sec63p are required in mice for adequate expression of a functional complex of the polycystic kidney disease gene products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate-limiting component of this complex and that there is a dose-response relationship between cystic dilation and levels of functional polycystin-1 following mutation of Prkcsh or Sec63. Reduced expression of polycystin-1 also serves to sensitize the kidney to cyst formation resulting from mutations in Pkhd1, the recessive polycystic kidney disease gene. Finally, we show that proteasome inhibition increases steady-state levels of polycystin-1 in cells lacking glucosidase II beta and that treatment with a proteasome inhibitor reduces cystic disease in orthologous gene models of human autosomal dominant polycystic liver disease.
  • Yasunobu Ishikawa, Saori Nishio, Hiroaki Sasaki, Risshi Kudo, Hideki Goto, Masanori Ito, Akira Suzuki, Yuichiro Fukazawa, Toshio Mochizuki, Takao Koike
    CLINICAL AND EXPERIMENTAL NEPHROLOGY 15 (1) 179 - 183 1342-1751 2011/02 [Refereed][Not invited]
    Transplantation-associated thrombotic microangiopathy (TA-TMA) is a rare but devastating syndrome that occurs in allogeneic hematopoietic stem cell transplant recipients, and is associated with a variety of transplantation-related factors, including conditioning regimens, immunosuppressive agents, graft-versus-host disease (GVHD) and opportunistic infections. TA-TMA has an unfavorable prognosis and responds poorly to conventional treatment including plasma exchange (PE). We present a case of a 37-year-old man with membranous nephropathy (MN) and polyserositis caused by GVHD after hematopoietic stem cell transplantation. He developed TA-TMA after steroid pulse therapy for polyserositis. We treated the patient with PE and mycophenolate mofetil (MMF) after which the TA-TMA successfully improved and the MN underwent complete remission. The present case suggests that corticosteroids with severe GVHD might increase the risk of TA-TMA, and that PE in combination with MMF may be a valuable therapy to improve the prognosis.
  • Vinita Takiar, Saori Nishio, Patricia Seo-Mayer, J. Darwin King, Hui Li, Li Zhang, Anil Karihaloo, Kenneth R. Hallows, Stefan Somlo, Michael J. Caplan
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108 (6) 2462 - 2467 0027-8424 2011/02 [Refereed][Not invited]
    Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion and abnormal proliferation of cyst-lining epithelial cells. The chloride channel of the cystic fibrosis transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug in wide clinical use, is a pharmacological activator of AMPK. We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo models of renal cystogenesis. In addition, metformin administration produces a significant decrease in the cystic index in two mouse models of ADPKD. Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD.
  • Sik Lee, Sarah Huen, Hitoshi Nishio, Saori Nishio, Heung Kyu Lee, Bum-Soon Choi, Christiana Ruhrberg, Lloyd G. Cantley
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 22 (2) 317 - 326 1046-6673 2011/02 [Refereed][Not invited]
    The ischemically injured kidney undergoes tubular cell necrosis and apoptosis, accompanied by an interstitial inflammatory cell infiltrate. In this study, we show that iNos-positive proinflammatory (M1) macrophages are recruited into the kidney in the first 48 hours after ischemia/reperfusion injury, whereas arginase 1- and mannose receptor positive, noninflammatory (M2) macrophages predominate at later time points. Furthermore, depletion of macrophages before ischemia/reperfusion diminishes kidney injury, whereas depletion at 3 to 5 days after injury slows tubular cell proliferation and repair. Infusion of Ifn gamma-stimulated, bone marrow-derived macrophages into macrophage-depleted mice at the time of kidney reperfusion restored injury to the level seen without macrophage depletion, suggesting that proinflammatory macrophages worsen kidney damage. In contrast, the appearance of macrophages with the M2 phenotype correlated with the proliferative phase of kidney repair. In vitro studies showed that IFN-gamma-stimulated, proinflammatory macrophages begin to express markers of M2 macrophages when cocultured with renal tubular cells. Moreover, IL-4 stimulated macrophages with an M2 phenotype, but not IFN gamma-stimulated proinflammatory macrophages, promoted renal tubular cell proliferation. Finally, tracking fluorescently labeled, IFN gamma-stimulated macrophages that were injected after injury showed that inflammatory macrophages can switch to an M2 phenotype in the kidney at the onset of kidney repair. Taken together, these studies show that macrophages undergo a switch from a proinflammatory to a trophic phenotype that supports the transition from tubule injury to tubule repair.
  • Saori Nishio, Xin Tian, Anna Rachel Gallagher, Zhiheng Yu, Vishal Patel, Peter Igarashi, Stefan Somlo
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 21 (2) 295 - 302 1046-6673 2010/02 [Refereed][Not invited]
    Polycystic kidney disease (PKD) can arise from either developmental or postdevelopmental processes. Recessive PKD, caused by mutations in PKHD1, is a developmental defect, whereas dominant PKD, caused by mutations in PKD1 or PKD2, occurs by a cellular recessive mechanism in mature kidneys. Oriented cell division is a feature of planar cell polarity that describes the orientation of the mitotic axes of dividing cells during development with respect to the luminal vector of the elongating nephron. In polycystic mutant mice, the loss of oriented cell division may also contribute to the pathogenesis of PKD. Here, we examined the role of oriented cell division in mouse models based on mutations in Pkd1, Pkd2, and Pkhd1. Precystic tubules after kidney-selective inactivation of either Pkd1 or Pkd2 did not lose oriented division before cystic dilation but lost oriented division after tubular dilation began. In contrast, Pkhd1(del4/de14) mice lost oriented cell division but did not develop kidney cysts. Increased intercalation of cells into the plane of the tubular epithelium maintained the normal tubular morphology in Pkhd1(de14/de14) mice, which had more cells present in transverse tubular profiles. In conclusion, loss of oriented cell division is a feature of Pkhd1 mutation and cyst formation, but it is neither sufficient to produce kidney cysts nor required to initiate cyst formation after mutation in Pkd1 or Pkd2.
  • Yoshihito Ohta, Lisa Fujimura, Saori Nishio, Masafumi Arima, Akemi Sakamoto, Hideaki Shimada, Takenori Ochiai, Takeshi Tokuhisa, Masahiko Hatano
    INTERNATIONAL JOURNAL OF ONCOLOGY 36 (2) 427 - 434 1019-6439 2010/02 [Refereed][Not invited]
    The BTB-kelch protein Nd1-L acts as an actin cytoskeleton stabilizer expressed ubiquitously in mouse tissues. We examined the effect of Nd1-L on cancer cell invasion and metastasis. Over-expression of Nd1-L in murine colon carcinoma cell line Colon 26 and murine melanoma cell line B16 resulted in suppression of pulmonary and liver metastasis after inoculation of these cells to syngeneric mice and in increased survival in an animal model. On the other hand, knock down of Nd1-L by RNA interference promoted metastasis ability of these cells. Increased expression of Nd1-L inhibited migration and Matrigel invasion capacity of cancer cell lines in vitro. Thus, Nd1-L expression inversely correlated with invasive and metastasis capacity of cancer cells. Furthermore, increased expression of Nd1-L in NIH3T3 cells inhibited growth factor induced activation of Rho family small GTPases such as Rho, Rac and cdc42. These results suggest that Nd1-L is involved in invasion and metastasis of cancer cells by regulating the actin cytoskeleton and Rho family proteins.
  • Kudo R, Hashimoto S, Sasaki H, Nakagaki T, Maoka T, Ishikawa Y, Nishio S, Mochizuki T, Koike T
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 11 98 (11) 2879 - 2881 0021-5384 2009/11 [Refereed][Not invited]
  • Naoki Watanabe, Kentaro Hiramatsu, Rieko Miyamoto, Kaoru Yasuda, Norihiko Suzuki, Naoko Oshima, Hiroshi Kiyonari, Dai Shiba, Saori Nishio, Toshio Mochizuki, Takahiko Yokoyama, Shoichi Maruyama, Seiichi Matsuo, Yuko Wakamatsu, Hisashi Hashimoto
    FEBS LETTERS 583 (12) 2108 - 2113 0014-5793 2009/06 [Refereed][Not invited]
    Glis3 is a member of the Gli-similar subfamily. GLIS3 mutations in humans lead to neonatal diabetes, hypothyroidism, and cystic kidney disease. We generated Glis3-deficient mice by gene-targeting. The Glis3(/) mice had significant increases in the basal blood sugar level during the first few days after birth. The high levels of blood sugar are attributed to a decrease in the Insulin mRNA level in the pancreas that is caused by impaired islet development and the subsequent impairment of Insulin-producing cell formation. The pancreatic phenotypes indicate that the Glis3-deficient mice are a model for GLIS3 mutation and diabetes mellitus in humans. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
  • Sekiya Shibazaki, Zhiheng Yu, Saori Nishio, Xin Tian, R. Brent Thomson, Michihiro Mitobe, Angeliki Louvi, Heino Velazquez, Shuta Ishibe, Lloyd G. Cantley, Peter Igarashi, Stefan Somlo
    HUMAN MOLECULAR GENETICS 17 (11) 1505 - 1516 0964-6906 2008/06 [Refereed][Not invited]
    Polycystic kidney disease (ADPKD) results from failure of the kidney to properly maintain three-dimensional structure after loss of either polycystin-1 or -2. Mice with kidney selective inactivation of Pkd1 during embryogenesis develop profound renal cystic disease and die from renal failure within 3 weeks of birth. In this model, cysts form exclusively from cells in which Cre recombinase is active, but the apparent pace of cyst expansion varies by segment and cell type. Intercalated cells do not participate in cyst expansion despite the presence of cilia up to at least postnatal day 21. Cystic segments show a persistent increase in proliferation as determined by bromodeoxyuridine (BrdU) incorporation; however, the absolute proliferative index is dependent on the underlying proliferative potential of kidney tubule cells. Components of the extracellular regulated kinase (MAPK/ERK) pathway from Ras through MEK1/2 and ERK1/2 to the effector P90(RSK) are activated in both perinatal Pkd1 and adult Pkd2 ortholgous gene disease models. The pattern of MAPK/ERK activation is focal and does not correlate with the pattern of active proliferation identified by BrdU uptake. The possibility of a causal relationship between ERK1/2 activation and cyst cell proliferation was assessed in vivo in the acute perinatal Pkd1 model of ADPKD using MEK1/2 inhibitor U0126. U0126 treatment had no effect on progression of cyst formation in this model at doses sufficient to reduce phospho-ERK1/2 in cystic kidneys. Cysts in ADPKD exhibit both increased proliferation and activation of MAPK/ERK, but cyst growth is not prevented by inhibition of ERK1/2 activation.
  • Yuji Matsudo, Yasuyuki Takamori, Lisa Fujimura, Saori Nishio, Kazushi Sasagawa, Issei Komuro, Takeshi Tokuhisa, Masahiko Hatano
    TRANSGENIC RESEARCH 15 (5) 573 - 581 0962-8819 2006/10 [Refereed][Not invited]
    Doxorubicin is one of the most effective drugs available for cancer chemotherapy. However, the clinical use of doxorubicin has been greatly limited because of severe side effects on cardiomyocytes. Since Nd1-L, a novel actin-binding protein, is expressed most abundantly in the heart of adult mice, we examined a role of Nd1-L in doxorubicin-induced cardiomyopathy. When doxorubicin (5 mg/kg x 4 times) was injected into adult mice at a 3-day-interval, approximately 50% of injected mice died within 4 weeks of the first injection. Nd1-L mRNA expression in the heart decreased within 3 weeks after the first injection and many cardiomyocytes of injected mice died by apoptosis. Overexpression of Nd1-L in the heart of transgenic mice protected the cardiomyocytes from apoptosis and improved survival rate after doxorubicin injection. Furthermore, activation of Erk1/2 was observed in cultured cells overexpressing Nd1-L. Thus, Nd1-L plays a critical role in protecting the heart from doxorubicin-induced cardiomyopathy.
  • S Nishio, M Hatano, M Nagata, S Horie, T Koike, T Tokuhisa, T Mochizuki
    JOURNAL OF CLINICAL INVESTIGATION 115 (4) 910 - 918 0021-9738 2005/04 [Refereed][Not invited]
    Autosomal dominant polycystic kidney disease (ADPKD) is the most common human monogenic genetic disorder and is characterized by progressive bilateral renal cysts and the development of renal insufficiency. The cystogenesis of ADPKD is believed to be a monoclonal proliferation of PKD-deficient (PKD-/-) renal tubular epithelial cells. To define the function of Pkd1, we generated chimeric mice by aggregation of Pkd1(-/-) ES cells and Pkd1(+/+) morulae from ROSA26 mice. As occurs in humans with ADPKD, these mice developed cysts in the kidney, liver, and pancreas. Surprisingly, the cyst epithelia of the kidney were composed of both Pkd1(-/-) and Pkd1(+/+) renal tubular epithelial cells in the early stages of cystogenesis. Pkd1(-/-) cyst epithelial cells changed in shape from cuboidal to flat and replaced Pkd1(-/-) cyst epithelial cells lost by JNK-mediated apoptosis in intermediate stages. In late-stage cysts, Pkd1(-/-) cells continued immortalized proliferation with downregulation of p53. These results provide a novel understanding of the cystogenesis of ADPKD patients. Furthermore, immortalized proliferation without induction of p53 was frequently observed in 3T3-type culture of mouse embryonic fibroblasts from Pkd1(-/-) mice. Thus, Pkd1 plays a role in preventing immortalized proliferation of renal tubular epithelial cells through the induction of p53 and activation of JNK.
  • K Horiuchi-Suzuki, A Konno, M Ueda, Y Fukuda, S Nishio, K Hashimoto, H Saji
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 31 (3) 388 - 398 1619-7070 2004/03 [Refereed][Not invited]
    In spite of recent advances in bone cellular and molecular biology, there is still a poor correlation between these parameters and data obtained from bone scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc-BPs) have long been recognised as bone-seeking agents with an affinity for areas of active mineralisation. However, during clinical trials with a pH-sensitive tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies (bone metastases, Paget's diseases) and lacked accumulation in normal mature bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular level was considered necessary. Moreover, to learn more about the role of Tc bone agents, acid-base regulation by bone tissue or cells was studied. First, biological parameters in body fluid were measured under systemic acidosis, induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)-bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a conventional Tc-BP agent were carried out. The effect of glucose-mediated acidification on the skeletal distribution of the Tc agents in the mice provided valuable hints regarding the differential mediation of bone cells in skeletal tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc-BP was screened under diverse acidification conditions. Moreover, studies were also carried out on acid-base parameters related to the cellular uptake mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the osteoclastic system was detected, and use of Tc(V)-DMS in the differential detection of osteoblastic and osteoclastic metastases is discussed.


  • NISHIO Saori  The Japanese journal of nephrology  54-  (4)  497  -500  2012/05/25  [Not refereed][Not invited]
  • 乳原 善文, 香村 衝一, 木村 理, 嶋村 剛, 田邉 一成, 土谷 健, 成田 一衛, 中西 浩一, 西尾 妙織, 奴田原 紀久雄, 村 信介, 花岡 一成, 東原 英二, 堀江 重郎, 武藤 智, 望月 俊雄  The Japanese journal of nephrology  53-  (4)  556  -583  2011/05/25  [Not refereed][Not invited]
  • ISHIKAWA Yasunobu, NISHIO Saori, CHIBA Takashi, SATO Akiko, KIMACHI Miho, IKENOUE Tatsuyoshi, NAKAGAKI Tasuku, NAKAZAWA Daigo, ITO Masanori, SHIBAZAKI Sekiya, MORITA Ken, NONOMURA Katsuya, KOIKE Takao  Nihon Toseki Igakkai Zasshi  44-  (2)  173  -179  2011/02/28  [Not refereed][Not invited]
    A 35-year-old man had undergone maintenance hemodialysis therapy since 1998, which however was switched to peritoneal dialysis because of blood access problems in 2000. He developed huge ectopic calcifications in the right shoulder and left buttock in December 2003 due to hyperphosphatemia and calcium-phosphate product above 90 (mg/dL)<SUP>2</SUP>. To improve hyperphosphatemia and ectopic calcifications, the dialysis modality was converted to hemodialysis in October 2004. However, the ectopic calcifications progressively worsened. He was referred to our hospital for kidney transplantation i...
  • KUDO Risshi, HASHIMOTO Seiji, SASAKI Hiroaki, NAKAGAKI Tasuku, MAOKA Tomochika, ISHIKAWA Yasunobu, NISHIO Saori, MOCHIZUKI Toshio, KOIKE Takao  Nihon Naika Gakkai Zasshi  98-  (11)  2879  -2881  2009/11/10  [Not refereed][Not invited]
    症例は76歳の男性.1995年より関節リウマチ及び関節リウマチに伴う器質化肺炎(BOOP)にて加療中であった.2008年1月に初めて顕微鏡的血尿を指摘され,その後急速な腎機能障害の進行を認め同年6月当科紹介初診となった.潜血の他,蛋白尿も認め急速進行性糸球体腎炎(RPGN)を疑い入院予定とした.しかしBOOPが急速に増悪し,近医にてステロイドの内服加療が開始された.その後徐々に腎機能は改善傾向を示し,入院時には腎機能は改善傾向を示し,尿蛋白の陰性化も認めた.経皮的腎生検を施行し,結果は半月体形成性糸球体腎炎(pauchi-immune type)であった.なおANCAは陰性であった.関節リウマチに関連する腎障害としては薬剤性やアミロイドーシスが有名であるが,腎炎そのものは稀とされる.さらに半月体形成性糸球体腎炎を示す少数の過去の報告例でもp-ANCA関連腎炎が大半を占める.また,BOOPと半月体形成性糸球体腎炎との合併例の報告は未だに無い.本例ではステロイドの加療によりBOOPと腎炎が同時に改善しているなど関節リウマチに伴う合併症を考察する上で稀少で示唆に富む症例と考えここに報告する.
  • 西尾 妙織  北海道醫學雜誌 = Acta medica Hokkaidonensia  79-  (6)  695  -703  2004/11/01  [Not refereed][Not invited]
  • 西尾 妙織, 柴崎 跡也, 山村 剛, 佐々木 直美, 山田 幹二, 河田 哲也, 小池 隆夫, 佐藤 英俊  Nihon Naika Gakkai Zasshi  90-  (2)  332  -334  2001/02/10  [Not refereed][Not invited]

Educational Activities

Teaching Experience

  • 医学総論
    開講年度 : 2019
    課程区分 : 博士後期課程
    開講学部 : 医学研究科

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