| Project/Area Number |
22390169
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
DOI Toshio 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60183498)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Hideharu 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60399342)
NAGAI Kojiro 徳島大学, 病院, 講師 (40542048)
MIMA Akira 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (00432401)
TOMINAGA Tatsuya 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80425446)
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| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
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| Keywords | BMP4 / 糖尿病性腎症 / Smad1 / Sox9 / バイオマーカー / 抗体医療 / BMP / ALK3/6 / 分子標的治療 |
|---|
| Research Abstract |
BMP4 directly regulated Smad1 signaling in vitro. Both BMP4 and phosphorylated Smad1 were expressed in association with mesangial matrix hyperplasia in diabetic kidney. BMP4 knock-in transgenic mice showed typical mesangial matrix increase as well as BMP4 expression after induction by tamoxifen. On the other hand, BMP4 knock-out (BMP4(+/-)) mice showed amelioration of glomerular matrix hyperplasia induced by streptozotocin. Furthermore, neutralizing antibody for BMP4 normalized glomerular matrix hyperplasia and phosphorylated Smad1 expression in glomeruli of diabetic mice. These results suggest that BMP4/Smad1 signaling plays the critical pathogenetic role for diabetic nephropathy.
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