Activin-follistatin system as atarget for the treatment of renal failure
| Project/Area Number |
15590842
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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 | Gunma University |
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Principal Investigator |
NOJIMA Yoshihisa Gunma University, Department of Medicine and Clinical Science, Professor, 大学院・医学系研究科, 教授 (90201699)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Itaru Gunma University, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (60143492)
HIROMURA Keiju Gunma University, Department of Medicine and Clinical Science, Assistant, 医学部, 助手 (70292597)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | activin / follistatin / renal regeneration / renal fibrosis / 線維芽細胞 / 形質転換 / 筋線維芽細胞 / 腎繊維化 / 繊維芽細胞 / 筋繊維芽細胞 |
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| Research Abstract |
The present study was conducted to examine the involvement of the activin-follistatin system in the fibrotic process of the kidney. Immunoreactive activin A was upregulated in tubular cells in the kidneys with unilateral ureteral obstruction but not in normal and contralateral kidneys. Activin A promoted cell proliferation, enhanced the expression of type I collagen mRNA, and induced the production of α-smooth muscle actin in a rat kidney fibroblast cell line (NRK-49F cells) as well as in primary cultured renal interstitial fibroblasts. In contrast, activin A did not affect the expressions of α-smooth muscle actin and type I collagen in renal epithelial tubular cell lines LLC-PK1, and MDCK. Follistatin, an antagonist of activin A, significantly inhibited cell proliferation in NRK-49F cells. Blockade of activin signaling by overexpression of truncated type II activin receptor, which lacked the intracellular kinase domain, decreased cell proliferation and reduced the expression level of type I collagen mRNA in NRK-49F cells. The expression of activin A was induced by TGF-^β1 or activin A itself. Induction of type I collagen expression by TGF-^β1 was reduced by follistatin or by overexpression of truncated type II activin receptor. These results suggest that activin A produced by tubular cells acts as a paracrine factor that activates renal interstitial fibroblasts during the fibrotic processes of the kidney.
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Report
(3 results)
Research Products
(12 results)
