Kimura Atsushi
| Faculty of Science Biological Sciences Reproductive and Developmental Biology | Professor |
Last Updated :2025/12/04
■Researcher basic information
Researchmap personal page
Researcher number
- 90422005
J-Global ID
Research Keyword
Educational Organization
- Bachelor's degree program, School of Science
- Master's degree program, Graduate School of Life Science
- Doctoral (PhD) degree program, Graduate School of Life Science
■Career
Career
■Research activity information
Papers
- Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-Running Activity in Rats.
Mai Otsuka, Yu Takeuchi, Maho Moriyama, Sakura Egoshi, Yuki Goto, Tingting Gu, Atsushi P Kimura, Shogo Haraguchi, Taishi Yoshii, Sakae Takeuchi, Makoto Matsuyama, George E Bentley, Sayaka Aizawa
Endocrinology, 166, 8, 10 Jun. 2025, [International Magazine]
English, Scientific journal, The objective of this study was to elucidate the role of endogenous Neuromedin U (NMU) in rats by performing NMU knockout (KO). Male, but not female NMU KO rats exhibited decreased wheel-running activity vs wildtype (WT), although overall home cage activity was not affected. Plasma testosterone in WT rats varied significantly over the course of a day, with a peak at ZT1 and a nadir at ZT18, whereas in NMU KO rats testosterone remained stable throughout the day. Chronic administration of testosterone restored wheel-running activity in NMU KO rats to the same level as in WT rats, suggesting that the decrease in wheel-running activity in NMU KO rats is due to the disruption of the diurnal change of testosterone. Accordingly, expression of the luteinizing hormone beta subunit (Lhb) mRNA in the pars distalis of anterior pituitary was significantly lower in NMU KO rats; immunostaining revealed that the size of luteinizing hormone (LH)-expressing cells was also relatively small in those animals. In the brain of male WT rats, Nmu was highly expressed in the pars tuberalis, and the NMU receptor Nmur2 was highly expressed in the ependymal cell layer of the third ventricle. This study reveals a novel function of NMU and indicates that endogenous NMU in rats plays a role in the regulation of motivated activity via regulation of testosterone. - Imeglimin modulates mitochondria biology and facilitates mitokine secretion in 3 T3-L1 adipocytes
Nobuhiko Takahashi, Atsushi P. Kimura, Takayuki Yoshizaki, Kazumasa Ohmura
Life Sciences, 122735, 122735, Elsevier BV, May 2024
Scientific journal - PTBP2 binds to a testis-specific long noncoding RNA, Tesra, and activates transcription of the Prss42/Tessp-2 gene
Josei Sato, Yui Satoh, Takehiro Yamamoto, Takehiro Watanabe, Shin Matsubara, Honoo Satake, Atsushi P. Kimura
Gene, 893, 147907, 147907, Elsevier BV, Jan. 2024
Scientific journal - A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen
Takumi Iwasaki, Megumi Tokumori, Misaki Matsubara, Fumiya Ojima, Kana Kamigochi, Sayaka Aizawa, Maho Ogoshi, Atsushi P. Kimura, Sakae Takeuchi, Sumio Takahashi
Molecular and Cellular Endocrinology, 577, 112044, 112044, Elsevier BV, Nov. 2023, [Peer-reviewed]
English, Scientific journal - Controlling the Rigidity of Kinesin-Propelled Microtubules in an In Vitro Gliding Assay Using the Deep-Sea Osmolyte Trimethylamine N-Oxide
Arif Md. Rashedul Kabir, Tasrina Munmun, Tomohiko Hayashi, Satoshi Yasuda, Atsushi P. Kimura, Masahiro Kinoshita, Takeshi Murata, Kazuki Sada, Akira Kakugo
ACS Omega, 7, 4, 3796, 3803, American Chemical Society ({ACS}), 01 Feb. 2022
Scientific journal - Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes.
Kai Otsuka, Hong Yang, Shin Matsubara, Akira Shiraishi, Misuzu Kurihara, Honoo Satake, Atsushi P Kimura
PloS one, 17, 8, e0273279, 2022, [International Magazine]
English, Scientific journal, A mouse testis-specific long noncoding RNA (lncRNA), Start, is localized in the cytosol of Leydig cells and in the nucleus of pachytene spermatocytes. We previously showed that Start regulates steroidogenesis through controlling the expression of Star and Hsd3b1 genes in Leydig cells, but its function in germ cells was not known. Here we verified that a spermatocyte-specific protease gene, Prss43/Tessp-3, was downregulated in Start-knockout testes. To investigate the transcriptional regulatory activity of Start in spermatocytes, we first performed a series of reporter gene assays using a thymidine kinase promoter in spermatocyte-derived GC-2spd(ts) cells. A 5.4-kb genome sequence encompassing Start exhibited enhancer activity for this promoter, and the activity was decreased by knockdown of Start. Deletion of the Start promoter and replacement of the Start sequence abolished the enhancer activity and, consistently, the activity was detected in further experiments only when Start was actively transcribed. We then examined whether the Prss43/Tessp-3 gene could be a target of Start. A reporter gene assay demonstrated that the 5.4-kb sequence exhibited enhancer activity for a Prss43/Tessp-3 promoter in GC-2spd(ts) cells and that the activity was significantly decreased by knockdown of Start. These results suggest that Start functions in transcriptional activation of the Prss43/Tessp-3 gene in spermatocytes. Given that Start is presumed to regulate steroidogenic genes at the posttranscriptional level in Leydig cells, the function in spermatocytes is a novel role of Start. These findings provide an insight into multifunctionality of lncRNAs in the testis. - A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells.
Kai Otsuka, Shin Matsubara, Akira Shiraishi, Natsumi Takei, Yui Satoh, Miho Terao, Shuji Takada, Tomoya Kotani, Honoo Satake, Atsushi P Kimura
Frontiers in endocrinology, 12, 665874, 665874, 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, The testis expresses many long noncoding RNAs (lncRNAs), but their functions and overview of lncRNA variety are not well understood. The mouse Prss/Tessp locus contains six serine protease genes and two lncRNAs that have been suggested to play important roles in spermatogenesis. Here, we found a novel testis-specific lncRNA, Start (Steroidogenesis activating lncRNA in testis), in this locus. Start is 1822 nucleotides in length and was found to be localized mostly in the cytosol of germ cells and Leydig cells, although nuclear localization was also observed. Start-knockout (KO) mice generated by the CRISPR/Cas9 system were fertile and showed no morphological abnormality in adults. However, in adult Start-KO testes, RNA-seq and qRT-PCR analyses revealed an increase in the expression of steroidogenic genes such as Star and Hsd3b1, while ELISA analysis revealed that the testosterone levels in serum and testis were significantly low. Interestingly, at 8 days postpartum, both steroidogenic gene expression and testosterone level were decreased in Start-KO mice. Since overexpression of Start in two Leydig-derived cell lines resulted in elevation of the expression of steroidogenic genes including Star and Hsd3b1, Start is likely to be involved in their upregulation. The increase in expression of steroidogenic genes in adult Start-KO testes might be caused by a secondary effect via the androgen receptor autocrine pathway or the hypothalamus-pituitary-gonadal axis. Additionally, we observed a reduced number of Leydig cells at 8 days postpartum. Collectively, our results strongly suggest that Start is a regulator of steroidogenesis in Leydig cells. The current study provides an insight into the overall picture of the function of testis lncRNAs. - A dual enhancer-silencer element, DES-K16, in mouse spermatocyte-derived GC-2spd(ts) cells.
Thusitha A M K Bandara, Kai Otsuka, Shin Matsubara, Akira Shiraishi, Honoo Satake, Atsushi P Kimura
Biochemical and biophysical research communications, 534, 1007, 1012, 26 Oct. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The multifunctionality of genome is suggested at some loci in different species but not well understood. Here we identified a DES-K16 region in an intron of the Kctd16 gene as the chromatin highly marked with epigenetic modifications of both enhancers (H3K4me1 and H3K27ac) and silencers (H3K27me3) in mouse spermatocytes. In vitro reporter gene assay demonstrated that DES-K16 exhibited significant enhancer activity in spermatocyte-derived GC-2spd(ts) and hepatic tumor-derived Hepa1-6 cells, and a deletion of this sequence in GC-2spd(ts) cells resulted in a decrease and increase of Yipf5 and Kctd16 expression, respectively. This was consistent with increased and decreased expression of Yipf5 and Kctd16, respectively, in primary spermatocytes during testis development. While known dual enhancer-silencers exert each activity in different tissues, our data suggest that DES-K16 functions as both enhancer and silencer in a single cell type, GC-2spd(ts) cells. This is the first report on a dual enhancer-silencer element which activates and suppresses gene expression in a single cell type. - Transcriptional activation of the mouse Scd2 gene by interdependent enhancers and long noncoding RNAs in ovarian granulosa cells.
Shota Mayama, Nobuhiko Hamazaki, Yuki Maruyama, Shin Matsubara, Atsushi P Kimura
The Journal of reproduction and development, 66, 5, 435, 444, 13 Oct. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Specific gene expression in granulosa cells is key for the function of ovary, but the molecular mechanism of transcriptional activation is not well studied. Here we investigated the regulatory mechanism of the mouse stearoyl-CoA desaturase 2 (Scd2) gene encoding an enzyme for lipid metabolism. Northern blot and in situ hybridization indicated that the mouse Scd2 mRNA was highly expressed in ovarian granulosa cells. We found four conserved noncoding sequences (CNSs) and two long noncoding RNAs (lncRNAs) transcribed from regions upstream of the Scd2 gene as candidates of regulatory elements/factors. These lncRNAs were predominantly transcribed in the opposite direction to Scd2 and localized in nuclei and showed the correlation with Scd2 expression, raising the possibility of their transcriptional regulatory roles. Indeed, knockdown of both lncRNAs, lncRNA-sc1 and lncRNA-sc2, significantly decreased the Scd2 mRNA level in primary granulosa cells. Then, we investigated the histone modification pattern at this locus by a chromatin immunoprecipitation assay, and two CNSs, CNS1 and CNS2, were found to be marked with high levels of histone H3K9/K27 acetylation in primary granulosa cells. By a reporter gene assay, both CNS1 and CNS2 interdependently exhibited enhancer activity for the Scd2 promoter in primary granulosa cells. These data suggest that the mouse Scd2 gene is activated by two lncRNAs and interdependent enhancers in ovarian granulosa cells, which provides a new insight into transcriptional activation in granulosa cells. - Knockdown of long noncoding RNA dreh facilitates cell surface GLUT4 expression and glucose uptake through the involvement of vimentin in 3T3-L1 adipocytes
Nobuhiko Takahashi, Atsushi P. Kimura, Kazumasa Ohmura, Sumiyoshi Naito, Mika Yoshida, Masahiro Ieko
Gene, 735, 144404, Elsevier {BV}, Apr. 2020, [Peer-reviewed]
Scientific journal - Dreh, a long noncoding RNA repressed by metformin, regulates glucose transport in C2C12 skeletal muscle cells.
Nobuhiko Takahashi, Atsushi P Kimura, Kai Otsuka, Kazumasa Ohmura, Sumiyoshi Naito, Mika Yoshida, Masahiro Ieko
Life sciences, 236, 116906, 116906, 01 Nov. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: The anti-hyperglycemic action of metformin on skeletal muscles is presently unclear. Long noncoding RNAs (lncRNAs) are implicated in multiple cellular functions. This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells. MAIN METHODS: Metformin accumulation was assessed using [14C]-metformin. A lncRNA array was used to investigate metformin-regulated lncRNAs in C2C12 skeletal muscle cells. Knockdown studies were applied to evaluate the function of lncRNA Dreh. A colorimetric assay was used for the measurement of medium glucose concentration; glucose transport was assessed using [3H]-2-deoxyglucose; real-time PCR was used for RNA expression analysis, and western blotting was used to assess protein expression in myotubes. A Dreh overexpression plasmid was transfected into the cells. KEY FINDINGS: Metformin accumulated in C2C12 myotubes. Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes. Knockdown of Dreh in the myotubes resulted in reduced glucose concentration in the culture medium, increased glucose transport, and increased levels of GLUT4 protein in the plasma membrane. Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes. SIGNIFICANCE: The glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells. Dreh is a novel regulator for glucose transport and could be a therapeutic target for diabetes. - A molecular mechanism of mouse placental spongiotrophoblast differentiation regulated by prolyl oligopeptidase.
Maruyama Y, Kimura AP
Zygote (Cambridge, England), 27, 1, 49, 53, Feb. 2019, [Peer-reviewed] - A novel testis-specific long noncoding RNA, Tesra, activates the Prss42/Tessp-2 gene during mouse spermatogenesis.
Satoh Y, Takei N, Kawamura S, Takahashi N, Kotani T, Kimura AP
Biology of reproduction, 100, 3, 833, 848, Oct. 2018, [Peer-reviewed] - Construction of artificial cilia from microtubules and kinesins through a well-designed bottom-up approach
Ren Sasaki, Arif Md. Rashedul Kabir, Daisuke Inoue, Shizuka Anan, Atsushi P. Kimura, Akihiko Konagaya, Kazuki Sada, Akira Kakugo
Nanoscale, 10, 14, 6323, 6332, Royal Society of Chemistry, 14 Apr. 2018, [Peer-reviewed]
English, Scientific journal - High-Sensitivity and High-Resolution in Situ Hybridization of Coding and Long Non-coding RNAs in Vertebrate Ovaries and Testes
Natsumi Takei, Takuma Nakamura, Shohei Kawamura, Yuki Takada, Yui Satoh, Atsushi P. Kimura, Tomoya Kotani
Biological Procedures Online, 20, 1, 6, BioMed Central Ltd., 01 Mar. 2018, [Peer-reviewed]
English, Scientific journal - A Testis-Specific Long Non-Coding RNA, lncRNA-Tcam1, Regulates Immune-Related Genes in Mouse Male Germ Cells
Misuzu Kurihara, Kai Otsuka, Shin Matsubara, Akira Shiraishi, Honoo Satake, Atsushi P. Kimura
FRONTIERS IN ENDOCRINOLOGY, 8, 299, Nov. 2017, [Peer-reviewed]
English, Scientific journal - Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes
Nobuhiko Takahashi, Atsushi P. Kimura, Sumiyoshi Naito, Mika Yoshida, Osamu Kumano, Takeshi Suzuki, Satoshi Itaya, Mitsuru Moriya, Masahiro Tsuji, Masahiro Ieko
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, 73, 4, 531, 538, Nov. 2017, [Peer-reviewed]
English, Scientific journal - A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells
Atsushi P. Kimura, Ryoma Yoneda, Misuzu Kurihara, Shota Mayama, Shin Matsubara
ENDOCRINOLOGY, 158, 11, 4105, 4121, Nov. 2017, [Peer-reviewed]
English, Scientific journal - Mouse prolyl oligopeptidase plays a role in trophoblast stem cell differentiation into trophoblast giant cell and spongiotrophoblast
Yuki Maruyama, Shin Matsubara, Atsushi P. Kimura
PLACENTA, 53, 8, 15, May 2017, [Peer-reviewed]
English, Scientific journal - A Genomic Region Transcribed Into a Long Noncoding RNA Interacts With the Prss42/Tessp-2 Promoter in Spermatocytes During Mouse Spermatogenesis, and Its Flanking Sequences Can Function as Enhancers
Ryoma Yoneda, Yui Satoh, Ikuya Yoshida, Shohei Kawamura, Tomoya Kotani, Atsushi P. Kimura
MOLECULAR REPRODUCTION AND DEVELOPMENT, 83, 6, 541, 557, Jun. 2016, [Peer-reviewed]
English, Scientific journal - Characterization of the human TCAM1P pseudogene and its activation by a potential dual promoter-enhancer: Comparison with a protein-coding mouse orthologue
Misuzu Kurihara, Atsushi P. Kimura
FEBS LETTERS, 589, 4, 540, 547, Feb. 2015, [Peer-reviewed]
English, Scientific journal - A Conserved Noncoding Sequence Can Function as a Spermatocyte-Specific Enhancer and a Bidirectional Promoter for a Ubiquitously Expressed Gene and a Testis-Specific Long Noncoding RNA
Misuzu Kurihara, Akira Shiraishi, Honoo Satake, Atsushi P. Kimura
JOURNAL OF MOLECULAR BIOLOGY, 426, 17, 3069, 3093, Aug. 2014, [Peer-reviewed]
English, Scientific journal - A long non-coding RNA transcribed from conserved non-coding sequences contributes to the mouse prolyl oligopeptidase gene activation
Shin Matsubara, Misuzu Kurihara, Atsushi P. Kimura
JOURNAL OF BIOCHEMISTRY, 155, 4, 243, 256, Apr. 2014, [Peer-reviewed]
English, Scientific journal - A testis-specific serine protease, Prss41/Tessp-1, is necessary for the progression of meiosis during murine in vitro spermatogenesis
Ryoma Yoneda, Atsushi P. Kimura
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 441, 1, 120, 125, Nov. 2013, [Peer-reviewed]
English, Scientific journal - A 914-bp promoter is sufficient to reproduce the endogenous prolyl oligopeptidase gene localization in the mouse placenta if not subject to position effect
Shin Matsubara, Yuki Maruyama, Atsushi P. Kimura
GENE, 524, 2, 114, 123, Jul. 2013, [Peer-reviewed]
English, Scientific journal - Three Testis-Specific Paralogous Serine Proteases Play Different Roles in Murine Spermatogenesis and Are Involved in Germ Cell Survival During Meiosis
Ryoma Yoneda, Takayuki Takahashi, Hitoshi Matsui, Naoharu Takano, Yuko Hasebe, Katsueki Ogiwara, Atsushi P. Kimura
BIOLOGY OF REPRODUCTION, 88, 5, 118, May 2013, [Peer-reviewed]
English, Scientific journal - Localization and subcellular distribution of prolyl oligopeptidase in the mouse placenta
Shin Matsubara, Takayuki Takahashi, Atsushi P. Kimura
JOURNAL OF MOLECULAR HISTOLOGY, 42, 3, 251, 264, Jun. 2011, [Peer-reviewed]
English, Scientific journal - Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
Kenji Moriyama, Atsuko Hanai, Kazuyuki Mekada, Atsushi Yoshiki, Katsueki Ogiwara, Atsushi Kimura, Takayuki Takahashi
Journal of Biomedical Science, 18, 1, 60, 60, Springer Science and Business Media LLC, 2011
Scientific journal - Expression of cyclooxygenase-2 and prostaglandin receptor EP4b mRNA in the ovary of the medaka fish, Oryzias latipes: Possible involvement in ovulation
Chika Fujimori, Katsueki Ogiwara, Akane Hagiwara, Sanath Rajapakse, Atsushi Kimura, Takayuki Takahashi
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 332, 1-2, 67, 77, Jan. 2011, [Peer-reviewed]
English, Scientific journal - Epigenetic patterns at the mouse prolyl oligopeptidase gene locus suggest the CpG island in the gene body to be a novel regulator for gene expression
Shin Matsubara, Takayuki Takahashi, Atsushi P. Kimura
GENE, 465, 1-2, 17, 29, Oct. 2010, [Peer-reviewed]
English, Scientific journal - Expression and localization of collagen type IV alpha 1 chain in medaka ovary
Yumiko Kato, Katsueki Ogiwara, Chika Fujimori, Atsushi Kimura, Takayuki Takahashi
CELL AND TISSUE RESEARCH, 340, 3, 595, 605, Jun. 2010, [Peer-reviewed]
English, Scientific journal - Two distinct localization patterns of testis-specific serine protease 1 (TESSP1) in the seminiferous tubules of the mouse testis.
Takano N, Kimura A, Takahashi T
Zoological science, 26, 4, 294, 300, Zoological Society of Japan, Apr. 2009, [Peer-reviewed]
English - Epigenetic activation of the human growth hormone gene cluster during placental cytotrophoblast differentiation
Atsushi P. Kimura, Daria Sizova, Stuart Handwerger, Nancy E. Cooke, Stephen A. Liebhaber
MOLECULAR AND CELLULAR BIOLOGY, 27, 18, 6555, 6568, Sep. 2007, [Peer-reviewed]
English, Scientific journal - Characterization of mouse tissue kallikrein 5
Sanath Rajapakse, Katsueki Ogiwara, Noriko Yamano, Atsushi Kimura, Kensaku Hirata, Sumio Takahashi, Takayuki Takahashi
ZOOLOGICAL SCIENCE, 23, 11, 963, 968, Nov. 2006, [Peer-reviewed]
English, Scientific journal - Tissue-specific chromatin modifications at a multigene locus generate asymmetric transcriptional interactions
Eung Jae Yoo, Isabela Cajiao, Jeong-Seon Kim, Atsushi P. Kimura, Aiwen Zhang, Nancy E. Cooke, Stephen A. Liebhaber
MOLECULAR AND CELLULAR BIOLOGY, 26, 15, 5569, 5579, Aug. 2006, [Peer-reviewed]
English, Scientific journal - Epigenetic modifications at the human growth hormone locus predict distinct roles for histone acetylation and methylation in placental gene activation
AP Kimura, SA Liebhaber, NE Cooke
MOLECULAR ENDOCRINOLOGY, 18, 4, 1018, 1032, Apr. 2004, [Peer-reviewed]
English, Scientific journal - Expression of Bradykinin B_2 Receptor in the Mouse Ovary(Physiology) :
Ohkura Ryuichi, Kimura Atsushi, Kihara Takahiro, Ogiwara Katsueki, Takahashi Takayuki
Zoological science, 20, 7, 847, 854, Zoological Society of Japan, 2003
English, The amounts of [1-5]-bradykinin in ovary extracts were determined using gonadotropin-treated immature female mice. The bradykinin levels in the ovary were high at 2, 6, and 48 hr after injection of human chorionic gonadotropin (hCG) into pregnant mare's serum gonadotropin (PMSG)-treated mice. Northern blot analysis of total RNAs isolated from the PMSG/hCG-treated mouse ovaries indicated that the B_2 receptor mRNA was constitutively expressed. Bradykinin B_2 receptor protein was detected by Western blot analysis of the ovary extracts. In situ hybridization analysis revealed that the B_2 receptor mRNA is expressed in the granulosa cells of all growing follicles of ovaries from both gonadotropin-treated immature and mature female mice. The effect of bradykinin on the expression of the B_2 receptor gene was examined by RT-PCR analysis with the ovary previously cultured in the presence of bradykinin. Bradykinin treatment of immature female, gonadotropin-treated immature female, and mature female mouse ovaries brought about no apparent changes in the B_2 receptor mRNA level. The present data indicate that the level of B_2 receptor expression in the ovary is fairly constant, and that the biological effect elicited by bradykinin in this organ may be dependent upon concentrations of the ligand produced by operation of the kinin-kallikrein system. - Molecular Cloning and Partial Characterization of Medaka Fish Stromelysin-3 and Its Restricted Expression in the Oocytes of Small Growing Follicles of the Ovary
Katsueki Ogiwara, Hitoshi Matsui, Atsushi Kimura, Takayuki Takahashi
Molecular Reproduction and Development, 61, 1, 21, 31, Jan. 2002, [Peer-reviewed]
English, Scientific journal - Localization of bradykinin B_2 receptor in the follicles of porcine ovary and increased expression of matrix metalloproteinase-3 and -20 in cultured granulosa cells by bradykinin treatment
KIMURA A, KIHARA T, OHKURA R, OGIWARA K, TAKAHASHI T
Biol Reprod, 65, 1462, 1470, 2001 - Structure and localization of the mouse prolyl oligopeptidase gene
KIMURA A, YOSHIDA I, TAKAGI N, TAKAHASHI T
J Biol Chem, 274, 24047, 24053, 1999
Other Activities and Achievements
- マウス精巣減数分裂過程の一次精母細胞における転写活性化機構
木村 敦, 佐藤 優衣, 丸山 優樹, 比較内分泌学, 44, 164, 58, 62, 03 Jun. 2018
日本比較内分泌学会, Japanese - マウス卵巣顆粒膜細胞でAmhr2遺伝子を活性化するlncRNA-Amhr2の発見
木村 敦, 比較内分泌学, 44, 164, 65, 68, 03 Jun. 2018
日本比較内分泌学会, Japanese - ヒト成長ホルモン遺伝子クラスターのLCRによる発現制御
木村 敦, COOKE Nancy E, LIEBHABER Stephen A, 日本比較内分泌学会ニュース = Newsletter of Japan Society for Comparative Endocrinology, 0, 122, 23, 31, 01 Aug. 2006
日本比較内分泌学会, Japanese - Molecular and biochemical characterization of a serine proteinase predominantly expressed in the medulla oblongata and cerebellar white matter of mouse brain
H Matsui, A Kimura, N Yamashiki, A Moriyama, M Kaya, Yoshida, I, N Takagi, T Takahashi, JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 15, 11050, 11057, Apr. 2000
English
Research Themes
- Studies on regulatory mechanisms underlying steroidogenic enzyme expression that governs sex differentiation, oocyte growth and maturation in teleost
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2026
井尻 成保, 木村 敦
本研究は、条鰭類全体の卵巣分化・発達を通したステロイドホルモン合成系の変化を、その代謝酵素の転写調節の面から明らかにする。卵黄形成時にはエストロゲンであるE2が、卵成熟時には卵成熟誘起ステロイドであるDHPが主に産生され、このE2からDHPへの産生転換は劇的に生じる。本研究ではその転写調節をFSHとLHの作用に焦点を当てて調べる。
E2産生を制御する律速酵素、アロマターゼをコードするcyp19a1遺伝子については、ティラピア、ウナギともにfoxl2、sf1の存在下でFSH刺激により最も高い転写活性が誘導されることが示された。ウナギについては、foxl2の働きを抑制する機構の存在が示唆された。
DHP産生の律速酵素である20β-HSDをコードするhsd17b12L遺伝子について、ウナギではこの遺伝子発現変化がDHP産生の調節要因ではないと結論された。チョウザメ、サクラマスではLHによる転写活性化は直接的ではなかったことから、他の因子の介在が考えられた。hsd17b12Lの転写を誘導する因子についてはサクラマスにおいて探索している。
ウナギではhsd17b12Lの転写活性化がDHP産生の制御要因ではないことから、その前駆体である17OHP産生機構に焦点を当てて調べ、プロゲステロンをアンドロステンジオンに代謝するcyp17a1の発現消失によって17OHPが産生されるということを強く示唆している。Cyp17a1遺伝子の発現を抑制する因子の存在が考えられ、その因子の同定を進めている。
以上の結果は、ステロイド代謝酵素はLH、FSHによる単純な発現調節ではなく、様々な転写因子が関わる複雑な調節機構であり、それぞれの酵素にそれぞれ異なった転写調節因子が関わっていることを示している。その機構はcyp19を除いてほとんど解っておらず、これを解明する意義は大きい。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K23696 - Studies on regulatory mechanisms underlying steroidogenic enzymes expression that governs sex differentiation, oocyte growth and maturation in teleost
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2026
井尻 成保, 木村 敦
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 22H02431 - An exploratory study of extracellular mitochondrial proteins as novel markers of insulin resistance.
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2025
高橋 伸彦, 木村 敦, 大村 一将
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Health Sciences University of Hokkaido, 22K07403 - A novel mechanism of spermatogenesis regulated by long noncoding RNA and multi-functional genome element
Grants-in-Aid for Scientific Research
01 Apr. 2020 - 31 Mar. 2024
木村 敦, 佐竹 炎
本研究は、精子形成の全容を理解することを目指して、一次精母細胞において長鎖非コードRNAと多機能性ゲノム（dual promoter-enhancer）が協働的に機能するという新しいメカニズムを、マウスを用いて検証するものである。計画の前半2年間では、まず精巣特異的長鎖非コードRNAであるlncRNA-HSVIIIノックアウトマウスの表現型解析を行うこととなっており、計画1年目では顕著な表現型をみつけることはできていなかった。これに対し、計画2年目である本年度は2カ月齢から12カ月齢のノックアウトマウスを解析することによってlncRNA-HSVIII欠損によると思われる表現型を見出した。具体的には、精子数が顕著に減少している個体がノックアウトのみで見出され、精巣切片の観察により異常な構造がノックアウトで顕著に多く見られることもわかった。さらに驚くべきことに、血中テストステロンレベルがノックアウトマウスで有意に減少していることも明らかになり、テストステロン合成に関わる複数の遺伝子の発現量がノックアウトマウスの精巣で減少していた。これらのことから、lncRNA-HSVIIIは生殖細胞のみならずライディッヒ細胞でも機能的であることが示唆される。一方、本年度は、lncRNA-HSVIII結合タンパク質の同定も進める予定であったが、COVID-19の影響もあって、昨年度準備したビオチン化lncRNA-HSVIIIと結合したタンパク質を得た段階で止まっている。環境が整えばすぐに質量分析を行う予定となっている。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20H03285 - An exploratory study of extracellular proteins as novel markers of organ-specific glucose dysmetabolism.
Grants-in-Aid for Scientific Research
01 Apr. 2019 - 31 Mar. 2022
TAKAHASHI Nobuhiko
This research aimed to explore the extracellular proteins in each organ that reflect glucose dysmetabolism for the application of laboratory testing. As a result, we obtained the list of such potential extracellular proteins in the skeletal muscle cells and adipocytes. In addition, we unexpectedly discovered that imeglimin, a novel oral anti-diabetic drug, facilitates glucose transport in adipocytes. These findings contribute to the pathogenesis of diabetes.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Health Sciences University of Hokkaido, 19K07871 - The investigation of long noncoding RNA in exosome as a marker for glucometabolism in organ
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
Takahashi Nobuhiko, KUMAGAI Kyoko, JURAKU Hiroko
In this research, we explored the roles of exosome-containing long noncoding RNAs in in each organ which is involved in the pathogenesis of glucose dysmetabolism such as diabetes for the application of clinical evaluation. As a result, we obtained the list of potential RNAs in the exosomes for the evaluation of insulin resistance in the skeletal muscle. In addition, we found that many lncRNAs are associated with insulin resistance in the skeletal muscle cells and adipocytes. Moreover, in search of metformin-affected lncRNAs, we discovered that lncRNA Dreh is implicated in the glucose transport in the skeletal muscle cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Health Sciences University of Hokkaido, 16K08939 - Genome-wide identification of multi-functional dual promoter-enhancers and thier physiological roles during mouse spermatogenesis
Grants-in-Aid for Scientific Research
01 Apr. 2015 - 31 Mar. 2019
KIMURA Atsushi, MATSUBARA Shin, SHIRAISHI Akira
Spermatogenesis is the process to generate mature sperms through three steps: mitosis, meiosis, and spermiogenesis. Here we investigated a mechanism by which many essential genes to meiosis are transcriptionally activated by genome-wide analyses of histone modifications and transcripts as well as by the reporter gene assay and genome editing. We found that a multi-functional genomic element, dual promoter-enhancer (DPE), plays important roles in transcriptional activation during meiosis. In addition, we showed the involvement of long noncoding RNAs in this transcriptional regulation.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 15H04317 - Does Diurodrilus form a new phylum?
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2015
KAJIHARA Hiroshi, SHIMANO Satoshi, KIMURA Atsushi
More than 20 animal phyla are known from minute environment between sand particles in beaches. A number of interstitial species are known in the phylum Annelida, a group that is mainly comprised of lugworms, earthworms, and leaches. At the onset of this study, 11 species in eight genera of interstitial annelids had been reported from Japanese waters. No representative of the genus Diurodrilus had been known in Japan, but there is an undescribed form in Ishikari Beach, Hokkaido. This study aimed to test the phylum affiliation of such interstitial annelids as Diurodrilus and Trilobodrilus, which was doubted by previous studies. The conclusion, however, was that both groups actually belong to the phylum Annelida.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 25650133 - The significance of and the mechanism underlying the genomic multi-functionality.
Grants-in-Aid for Scientific Research
2009 - 2010
KIMURA Atsushi
I investigated whether the functional regions that we identified before at three mouse gene loci have different roles in different tissues. I found that some of the regions showed different activities to regulate gene transcription in different tissues. This difference is probably attributed to the epigenetic status and the transcription of the regulatory sequence itself.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 21770068 - Identification and characterization of functional genomic regions in reproductive organs
Grants-in-Aid for Scientific Research
2007 - 2008
KIMURA Atsushi
哺乳類の生殖器官におけるゲノム機能を明らかにするために、卵巣と精巣でクロマチンの緩んでいるゲノム領域を探索した。その結果、生殖器官で発現する遺伝子の転写をコントロールすると思われる新規の配列が複数同定できた。その中でも特に卵巣の顆粒膜細胞特異的に発現するAmhr2遺伝子座においては2つの機能領域が同定され、それぞれが組織によって異なる転写調節活性を持つことが示唆された。このことからこれらのゲノム領域が多機能である可能性が考えられた。
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 19770048
