| Project/Area Number |
21591033
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
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)
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| Co-Investigator(Kenkyū-buntansha) |
AKIYAMA Haruhiko 京都大学, 医学研究科, 准教授 (60402830)
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| Co-Investigator(Renkei-kenkyūsha) |
KISHI Seiji 徳島大学, 病院, 助教 (10519507)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 糖尿病性腎症 / Sox9 / Smad1 / BMP4 / 軟骨細胞様形質変化 / 不可逆的腎機能低下 / ALK3/6 / Scleraxis / HIF1 / ALK3 / 6 |
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| Research Abstract |
Advanced glycation end products induced the expression of chondrocyte marker proteins downstream from the BMP4-Smad1 signaling pathway in MCs. In addition, hypoxia also induced the expression of HIF-1, and chondrocyte markers. Overexpression of SOX9 caused ectopic expression of chondrocyte markers. Glomerular expressions of HIF-1, BMP4, and chondrocyte markers were observed in diabetic nephropathy mice. SOX9 was colocalized with HIF-1 in diabetic glomeruli. BMP4 knock-in transgenic mice showed not only similar pathological lesions to DN, but also the induction of chondrocyte markers in the sclerotic lesions. HIF-1 and BMP4 induce SOX9 expression and subsequent chondrogenic phenotype change in DN. The results suggested that the transdifferentiation of MCs into chondrocyte-like cells in chronic hypoxic stress may result in irreversible structural change in DN.
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