| Project/Area Number |
23591202
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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 | Jikei University School of Medicine |
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Principal Investigator |
MIYAZAKI Yoichi 東京慈恵会医科大学, 医学部, 准教授 (60266690)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Noggin / podocyte / proximal tubule / cross-talk / nephron / BMP / ネフロン / 細胞間クロストーク / MMP / VEGF / Diabetic nephropathy |
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| Research Abstract |
We established the transgenic mouse line (Podocine-rtTA; TetO-Noggin), in which Noggin, Bmp inhibitor, was selectively expressed only in the podocytes under the control of Dox. We then analyzed the adult transgenic mice with or without Dox for 3 months. Podocine-rtTA; TetO-Noggin with Dox showed a reduced expression of TG-lectin expression in proximal tubules, interstitial edema and a decrease in proximal tubular cells positive for phosphorylated Smad1/5/8. In contrast, the morphology of glomerulus appeared normal. It has been shown that BMP7-receptor, but not BMP per se, is not expressed in proximal tubules. Conditional knockout of Bmp7 in podoccytes has been reported to lead to a defect in proximal tubule development during embryonic stage. In conjunction with these findings, we assume that, in adulthood also, the podocyte injury cause not only the development of glomerulosclerosis, but also a damage in proximal tubules via a decrease of BMP expression.
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