| Project/Area Number |
15590869
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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 |
OKUDA Seiya KURUME UNIVERSITY, FACULTY OF MEDICINE THE THIRD DEPARTMENT OF INTERNAL MEDICINE, PROFESSOR, 医学部, 教授 (80158823)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAKI Kiyosi KURUME UNIVERSITY, FACULTY OF MEDICINE THE THIRD DEPARTMENT OF INTERNAL MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (10312141)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Growth factor / TGF-β / Soluble receptor / Glomerulosclerosis / Renal fibrosis / matrix / TGF-β acctivation / LTBP |
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| Research Abstract |
The extracellular domain of TGF-β type 2 receptor can bind active TGF-β tightly but does not involve signal transduction of TGF-β. Therefore, a large amount of TGF-β soluble receptor can prevent TGF-β binding to true TGF-β receptor. To investigate the effects of TGF-β soluble receptor on TGF-β action in vivo, the gene of TGF-β type 2 receptor extracellular domain was transfected into the muscle of rats by using 5x10^8 recombinant adenovirus vector at 1 days before the unilateral uretal obstruction. Serum concentration of TGF-β soluble receptor was quantitated by ELISA assay. The serum concentration of the soluble receptor at 10 days after the transfection was 70ng/ml, which was 50-fold higher than reported concentration of active form TGF-β in rats serum and considered to be sufficient to block the active TGF-β in vivo. Tubular damage and interstitial fibrosis were marked in ureteral obstruction rat kidney. These lesions were attenuated by the elevated level of the TGF-β soluble receptor. Interstitial fibronectin accumulation, vimentin expression and macrophage accumulation were markedly decreased by the TGF-β soluble receptor gene tranfection. TGF-β type 2 soluble receptor is a potent inhibitor of TGF-β to modulate renal fibrosis.
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