Roles of humoral factors and organ-organ or cell-cell communications in the development and progression of metabolic kidney diseases
| Project/Area Number | 26461226 |
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
MUKOYAMA Masashi 熊本大学, 大学院生命科学研究部(医), 教授 (40270558)
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| Co-Investigator(Renkei-kenkyūsha) |
MORI Kiyoshi 静岡県立大学, 薬学部, 特任教授 (60343232)
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| Research Collaborator |
KUWABARA Takashige 熊本大学, 大学院生命科学研究部, 助教 (00393356)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed(Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost : ¥3,800,000、Indirect Cost : ¥1,140,000)
Fiscal Year 2016 : ¥1,040,000 (Direct Cost : ¥800,000、Indirect Cost : ¥240,000)
Fiscal Year 2015 : ¥1,950,000 (Direct Cost : ¥1,500,000、Indirect Cost : ¥450,000)
Fiscal Year 2014 : ¥1,950,000 (Direct Cost : ¥1,500,000、Indirect Cost : ¥450,000)
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| Keywords | 腎臓学 / 内分泌学 / メタボリック症候群 / 糖尿病性腎症 / レニン・アンジオテンシン系 / ナトリウム利尿ペプチド / N型カルシウムチャネル / 自然炎症 / 高血圧 / アルドステロン / マクロファージ / metabolic syndrome / 肥満症 / renin-angiotensin system |
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| Outline of Final Research Achievements |
Lifestyle-related noncommunicable diseases such as diabetes, obesity and hypertension are the major risk for metabolic kidney diseases, in which endocrine dysregulation in organ-organ or cell-cell communications in the kidney may be suggested. We investigated roles of humoral factors in this pathophysiology.
We found that the natriuretic peptide (ANP and BNP) receptor GC-A in podocytes is important in protecting against aldosterone-induced glomerular injury in mice. We also found the role of N-type calcium channels in sympathetic nerve activation and podocyte injury in obese diabetic mice with nephropathy. Finally, we found the pathogenic role of local homeostatic inflammation driven by toll-like receptor 4 and its endogenous ligand myeloid-related protein 8 (MRP8), a macrophage-derived proinflammatory factor, in mouse models of diabetes-hyperlipidemia as well as proliferative nephritis. These findings may provide potential therapeutic strategies for metabolic kidney diseases.
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Report
(4results)
Research Products
(56results)
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[Journal Article] Natriuretic peptide receptor guanylyl cyclase-A pathway counteracts glomerular injury evoked by aldosterone through p38 mitogen-activated protein kinase inhibition.2017
Author(s)
Y. Kato, K. Mori, M. Kasahara, K. Osaki, A. Ishii, K.P. Mori, N. Toda, S. Ohno, T. Kuwabara, T. Tokudome, I. Kishimoto, M.A. Saleem, T. Matsusaka, K. Nakao, M. Mukoyama, M. Yanagita, H. Yokoi
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Journal Title
Scientific Reports
Volume : 7
Pages : 46624-46624
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] O-linked β-N-acetylglucosamine modification of proteins is essential for foot process maturation and survival in podocytes.2017
Author(s)
Ono S, Kume S, Yasuda-Yamahara M, Yamahara K, Takeda N, Chin-Kanasaki M, Araki H, Sekine O, Yokoi H, Mukoyama M, Uzu T, Araki SI, Maegawa H.
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Journal Title
Nephrol Dial Transplant.
Volume : 未定
Pages : 000-000
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.2016
Author(s)
Jun Morinaga, Tsuyoshi Kadomatsu, Keishi Miyata, Motoyoshi Endo, Kazutoyo Terada, Zhe Tian, Taichi Sugizaki, Hiroki Tanigawa, Jiabin Zhao, Shunshun Zhu, Michio Sato, Kimi Araki, Ken-ichi Iyama, Kengo Tomita, Masashi Mukoyama, Kimio Tomita, Kenichiro Kitamura, Yuichi Oike
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Journal Title
Kidney International
Volume : 89
Pages : 327-341
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model.2016
Author(s)
Yuki Narita, Miki Ueda, Kohei Uchimura, Yutaka Kakizoe, Yoshikazu Miyasato, Teruhiko Mizumoto, Jun Morinaga, Manabu Hayata, Terumasa Nakagawa, Masataka Adachi, Taku Miyoshi, Yoshiki Sakai, Daisuke Kadowaki, Sumio Hirata, Masashi Mukoyama, Kenichiro Kitamura
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Journal Title
Journal of Pharmacological Sciences
Volume : 130
Pages : 110-116
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] MicroRNA-26a inhibits TGF-β-induced extracellular matrix expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy.2015
Author(s)
Koga K, Yokoi H, Mori K, Kasahara K, Kuwabara T, Imamaki H, Ishii A, Mori KP, Kato Y, Ohno S, Toda N, Saleem MA, Sugawara A, Nakao K, Yanagita M, Mukoyama M.
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Journal Title
Diabetologia
Volume : 58
Pages : 2169-80
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The serine protease inhibitor camostat mesilate attenuates the progression of chronic kidney disease through its antioxidant effects.2015
Author(s)
Miki Ueda, Kohei Uchimura, Yuki Narita, Yoshikazu Miyasato, Teruhiko Mizumoto, Jun Morinaga, Manabu Hayata, Yutaka Kakizoe, Masataka Adachi, Taku Miyoshi, Naoki Shiraishi, Daisuke Kadowaki, Y Sakai, Masashi Mukoyama, Kenichiro Kitamura
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Journal Title
Nephron
Volume : 129
Pages : 223-232
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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