Molecular mechanisms of mesangial matrix expansion in the progression of diabetic nephropathy
| Project/Area Number |
25461221
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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 | Kyoto University |
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Principal Investigator |
Matsubara Takeshi 京都大学, 医学(系)研究科(研究院), 講師 (90422964)
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| Co-Investigator(Renkei-kenkyūsha) |
YANAGITA Motoko 京都大学, 大学院医学研究科・腎臓内科学, 教授 (70378769)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 病理学 / 糖尿病性腎症 |
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| Outline of Final Research Achievements |
Diabetic nephropathy is pathologically characterized by the accumulation of extracellular matrix in the mesangium, of which the main component is α1/α2 type IV collagen (Col4). Recently, we identified Smad1 as a direct regulator of Col4 under diabetic conditions in vitro. Here, we demonstrate that Smad1 plays a key role in diabetic nephropathy through bone morphogenetic protein 4 (BMP4) in vivo. Smad1-overexpressing mice were established, and the induction of diabetes resulted in greater mesangial expansion. We also identified BMP4 as a regulatory factor of Smad1 in diabetic nephropathy and showed that diabetic mice treated with a BMP4-neutralizing antibody exhibited decreased Smad1 phosphorylation and less mesangial expansion than those with control IgG. Our data indicate that BMP4/Smad1 signaling is a critical cascade for the progression of mesangial expansion and that blocking this signal could be a novel therapeutic strategy for diabetic nephropathy.
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in the Development of Diabetic Nephropathy.2015
Author(s)
Matsubara T, Araki M, Abe H, Ueda O, Jishage K, Mima A, Goto C, Tominaga T, Kinosaki M, Kishi S, Nagai K, Iehara N, Fukushima N, Kita T, Arai H, Doi T.
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Journal Title
Diabetes
Volume: ６４
Issue: 8
Pages: 2978-2990
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease2015
Author(s)
Nakagawa S, Nishihara K, Miyata H, Shinke H, Tomita E, Kajiwara M, Matsubara T, Iehara N, Igarashi Y, Yamada H, Fukatsu A, Yanagita M, Matsubara K & Masuda S
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Journal Title
PLoS One
Volume: 10
Issue: 8
Pages: 1-14
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Clinical features and treatment of multicentric castleman's disease : a retrospective study of 21 Japanese patients at a single institute.
Author(s)
Kawabata H, Kadowaki N, Nishikori M, Kitawaki T, Kondo T, Ishikawa T, Yoshifuji H, Yamakawa N, Imura Y, Mimori T, Matsumura Y, Miyachi Y, Matsubara T, Yanagita M, Haga H, Takaori-Kondo A.
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Journal Title
J Clin Exp Hematop.
Volume: 53(1)
Pages: 69-77
NAID
Related Report
Peer Reviewed
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[Book] 最新透析医療2015
Author(s)
松原 雄、武藤 学、柳田素子
Total Pages
859
Publisher
医歯薬ジャーナル社
Related Report
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