2013 Fiscal Year Annual Research Report
| Project/Area Number |
21229013
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| Research Institution | Kyoto University |
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Principal Investigator |
中尾 一和 京都大学, 医学(系)研究科(研究院), 教授 (00172263)
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| Co-Investigator(Kenkyū-buntansha) |
八十田 明宏 京都大学, 医学(系)研究科(研究院), 講師 (50378642)
海老原 健 京都大学, 医学(系)研究科(研究院), 准教授 (70362514)
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| Project Period (FY) |
2009-05-11 – 2014-03-31
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| Keywords | ホルモン / 間葉系 / 内分泌 / レプチン / CNP |
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| Research Abstract |
ナトリウム利尿ペプチド、血管
(CNP/GC-B)(骨格系) 軟骨特異的CNP及びGC-B KOマウスを作製、CNP/GC-Bの軟骨局所因子として骨伸長での重要性を証明した。(心血管系)血管内皮特異的CNPKOマウスで血管内皮由来CNPの血圧制御を詳細に解析した。(中枢神経系) 中枢神経系特異的CNP KOを作、中枢神経系CNPの高脂肪食体重増加での意義を示した。(ANP･BNP/GC-A) (心血管系) 肺高血圧モデルマウス作成に成功、TRPC6/3阻害薬肺高血圧改善効果を見出した。(proBNP)我々の開発した新規ヒトproBNP特異的測定法で血液透析前後での血中proBNPの動態を解明した。（腎臓）アルドステロン投与GC-A KOマウス糸球体内細胞のアポトーシス増加に対してp38MAPK阻害の抑制作用を明らかにした。(血管細胞発生分化) 昨年度までに確立した血管構成細胞分化誘導・単離法で疾患iPS細胞を用いたもやもや病の病態解析に成功した。
レプチン系
(レプチン抵抗性) 肥満無しでレプチン抵抗性を示す動物モデルを確立、脳内シグナルを詳細に解析した。(脂肪毒性)著明な脂肪肝を呈するレプチン欠損ラットで肝臓レプチン反応遺伝子を明らかにした。セイピン欠損ラットで脂肪萎縮発症メカニズムを明らかにした。(レプチン臨床)脂肪萎縮症へのレプチン補充治療薬事承認後も、製造承認、薬価収載に至り、世界で初めての臨床応用を日本で実現した。その長期安全性、有効性、合併症、予後に及ぼす効果を検討した。（脂肪細胞発生分化）ヒトiPS・ES細胞由来脂肪細胞が脂肪細胞機能を備え、移植後の生着・維持を明らかにした。先天性・後天性脂肪萎縮症患者iPS細胞の樹立した。
間葉系新規ホルモン探索
高脂肪食負荷ラットの脂肪組織からペプチド画分を調整、複数の既知生理活性ペプチドを同定した。
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| Current Status of Research Progress |
Reason
25年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
25年度が最終年度であるため、記入しない。
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[Journal Article] Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like receptor 4 signaling in diabetic nephropathy2014
Author(s)
Kuwabara, T., Mori, K., Mukoyama, M., Kasahara, M., Yokoi, H., Nakao, K.
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Journal Title
Clinical and Experimental Nephrology
Volume: impress
Pages: -
DOI
Peer Reviewed
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[Journal Article] Complexity of molecular forms of B-type natriuretic peptide in heart failure2013
Author(s)
Nishikimi, T., Kuwahara, K., Nakagawa, Y., Kangawa, K., Minamino, N., Nakao, K
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Journal Title
Heart
Volume: 99(10)
Pages: 677-679
Peer Reviewed
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[Journal Article] Angiotensin II type 1a receptor signalling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy2013
Author(s)
Yasuno, S., Kuwahara, K., Kinoshita, H., Yamada, C., Nakagawa, Y., Usami, S., Kuwabara, Y., Ueshima, K., Harada, M., Nishikimi, T., Nakao, K.
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Journal Title
British Journal of Pharmacology
Volume: 170(7)
Pages: 1384-1395
DOI
Peer Reviewed
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[Journal Article] Adrenomedullin in cardiovascular disease: A useful biomarker, its pathological roles and therapeutic application2013
Author(s)
Nishikimi, T., Kuwahara, K., Nakagawa, Y., Kangawa, K., Nakao, K.
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Journal Title
Current Protein and Peptide Science
Volume: 14(4)
Pages: 256-267
DOI
Peer Reviewed
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[Journal Article] Increased expression of HCN channels in the ventricular myocardium contributes to enhanced arrhythmicity in mouse failing hearts.2013
Author(s)
Kuwabara, Y., Kuwahara, K., Takano, M., Kinoshita, H., Arai, Y., Yasuno, S., Nakagawa, Y., Igata, S., Usami, S., Minami, T., Yamada, Y., Nakao, K., Yamada, C., Shibata, J., Nishikimi, T., Ueshima, K., Nakao, K.
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Journal Title
Journal of the American Heart Association
Volume: 2(3)
Pages: e000150
DOI
Peer Reviewed
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[Journal Article] Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: rationale and design of the ASsessment of clinical Usefulness in CKD patients with Atorvastatin (ASUCA) trial.2013
Author(s)
Ueshima, K., Kasahara, M., Koya, D., Babazono, T., Sato, T., Imamoto, M., Yasuno, S., Fujimoto, A., Tanaka, S., Kimura, G., Nakao, K.
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Journal Title
Clinical and experimental nephrology
Volume: 17(2)
Pages: 211-217
DOI
Peer Reviewed
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[Journal Article] Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3,4-dideoxyglucosone-3-ene in mice2013
Author(s)
Yokoi, H., Kasahara, M., Mori, K., Kuwabara, T., Toda, N., Yamada, R., Namoto, S., Yamamoto, T., Seki, N., Souma, N., Yamaguchi, T., Sugawara, A., Mukoyama, M., Nakao, K.
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Journal Title
Peritoneal Dialysis International
Volume: 33(2)
Pages: 143-154
DOI
Peer Reviewed
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[Journal Article] Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure2013
Author(s)
Nishikimi, T., Okamoto, H., Nakamura, M., Ogawa, N., Horii, K., Nagata, K., Nakagawa, Y., Kinoshita, H., Yamada, C., Nakao, K., Minami, T., Kuwabara, Y., Kuwahara, K., Masuda, I., Kangawa, K., Minamino, N., Nakao, K.
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Journal Title
PLoS ONE
Volume: 8(1)
Pages: e53233
DOI
Peer Reviewed
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[Journal Article] Human induced pluripotent stem cells differentiated into chondrogenic lineage via generation of mesenchymal progenitor cells2013
Author(s)
Koyama, N., Miura, M., Nakao, K., Kondo, E., Fujii, T., Taura, D., Kanamoto, N., Sone, M., Yasoda, A., Arai, H., Bessho, K., Nakao, K.
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Journal Title
Stem Cells and Development
Volume: 22(1)
Pages: 102-113
DOI
Peer Reviewed
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[Journal Article] Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver.2013
Author(s)
M. Aizawa-Abe, K. Ebihara, C. Ebihara, T. Mashimo, A. Takizawa, T. Tomita, T. Kusakabe, Y. Yamamoto, D. Aotani, S. Yamamoto-Kataoka, T. Sakai, K. Hosoda, T. Serikawa, K. Nakao
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Journal Title
Physiol Genomics.
Volume: 45(17)
Pages: 786-793
DOI
Peer Reviewed
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[Journal Article] Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production2013
Author(s)
S. H. Chew, Y. Okazaki, H. Nagai, N. Misawa, S. Akatsuka, K. Yamashita, L. Jiang, Y. Yamashita, M. Noguchi, K. Hosoda, Y. Sekido, T. Takahashi, S. Toyokuni
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Journal Title
Carcinogenesis
Volume: 35(1)
Pages: 164-172
DOI
Peer Reviewed
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[Journal Article] In vitro characterization and engraftment of adipocytes derived from human induced pluripotent stem cells and embryonic stem cells.2013
Author(s)
M. Noguchi, K. Hosoda, E. Mori, M. Nakane, K. Nakao, D. Taura, Y. Yamamoto, T. Kusakabe, M. Sone, H. Sakurai, J. Fujikura, K. Ebihara, K. Nakao
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Journal Title
Stem Cells and Development
Volume: 22(21)
Pages: 2895-2905
DOI
Peer Reviewed
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[Journal Article] Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.2013
Author(s)
N. Yamada-Goto, G. Katsuura, K. Ebihara, M. Inuzuka, Y. Ochi, Y. Yamashita, T. Kusakabe, A. Yasoda, N. Asahara-Satoh, H. Ariyasu, K. Hosoda, K. Nakao.
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Journal Title
Diabetes
Volume: 62(5)
Pages: 1500-1504
DOI
Peer Reviewed
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[Journal Article] The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431)2013
Author(s)
Hitomi T, Habu T, Kobayashi H, Okuda H, Harada KH, Osafune K, Taura D, Sone M, Asaka I, Ameku T, Watanabe A, Kasahara T, Sudo T, Shiota F, Hashikata H, Takagi Y, Morito D, Miyamoto S, Nakao K, Koizumi A
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Journal Title
Biochem Biophys Res Commun.
Volume: 439(4)
Pages: 419-426
DOI
Peer Reviewed
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[Journal Article] Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients.2013
Author(s)
Hitomi T, Habu T, Kobayashi H, Okuda H, Harada KH, Osafune K, Taura D, Sone M, Asaka I, Ameku T, Watanabe A, Kasahara T, Sudo T, Shiota F, Hashikata H, Takagi Y, Morito D, Miyamoto S, Nakao K, Koizumi A.
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Journal Title
Biochem Biophys Res Commun.
Volume: 438(1):
Pages: 13-19
DOI
Peer Reviewed
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