| Project/Area Number |
12671058
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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 | Kurume University |
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Principal Investigator |
KOHNO Keisuke KURUME UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF NEPHROLOGY, ASSISTANT PROFESSOR, 医学部, 助手 (70258416)
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| Co-Investigator(Kenkyū-buntansha) |
OKUDA Seiya KURUME UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80158823)
TAMAKI Kiyoshi KURUME UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (10312141)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Growth factor / TGF-β / Smad / peritoneal fibrosis / Adenovirus-vector / CAPD / Smad binding element / 細胞外マトリックス / 線維化 / 遺伝子導入 |
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| Research Abstract |
TGF-β1 plays a pathological role in fibrotic and sclerotic diseases including peritoneal fibrosis. Smads have been identified as pivotal components in TGF-** intracellular signaling. The present study was carried out to investigate TGF-β-induced Smad activation in cultured cells and experimental peritoneal firotic diseases in rodents. In cultured! cells, TGF-β1 induced phosphorylation of Smad2.Gene transfer using Adenovirus-vector, double-overexpression of Smad2 and Smad4 induced TGF-I3istimulated plasminogen activator inhibitor-1 (PM-i) expression more than overexpression of each Smad alone. Furthermore, overexpression of Smad7, one of inhibitory Smads, but not Smd6 reversed TGF- β1-inhibited cell proliferation by inhibiting Smad2 phosphorylation. In addition, TGF-β1 or high glucose condition induced the expression of SBE (Smad-binding element)-luciferase activity, which was reversed by the transfection-with Smad2 mutant or inhitory Smad7.
In experimental peritoneal fibrosis using iodine, progressive peritoneal thickness was observed. This thickness was due to the accumulation of matrix proteins. We tried gene transfer of Smad protein into these animal models. But the peritonea! fibrosis was not reproducible. We are now under investigation to make reproducible model of peritoneal fibrosis. However, our results indicate the possibility that modulation of Smad activity may attenuate the development of peritoneal fibrosis and sclerosis.
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