ROLE OF AND REGULATION OF GROWTH FACTOR TGF-β IN GLOMERULAR LESIONS
| 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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Report
(3 results)
Research Products
(22 results)
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[Journal Article] AGEs activate mesangial TGF-b-Smad signaling via an anguiotensin II type I receptor interaction.2004
Author(s)
Fukami K, Ueda S, Yamagishi S, Kato S, Inagami Y, Takeuchi M, Motomiya Y, Bucala R, Iida Y, Tamaki K, Imaizumi T, Cooper ME, Okuda S
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Journal Title
Kidney Int 66
Pages: 2137-2147
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Risk factors for renal glomerular and vascular changes in an autpsy-based population survey : The Hisayama study2003
Author(s)
Kubo M, Kiyohara Y, Kato I, Tanizaki Y, Katafuchi R, Hirakata H, Okuda S, Tsuneyoshi M, Sueishi K, Fujishima M, Iida M
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Journal Title
Kidney Int 63
Pages: 1508-1515
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Caveolae integration of growth factor receptor in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis.2001
Author(s)
Tamai O, Oka N, Kikuchi T, Koda Y, Soejima M, Wada Y, Fujisawa M, Tamaki K, Kawachi H, Shimizu F, Kimura H, Imaizumi T, Okuda S
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Journal Title
Kidney Int 59
Pages: 471-480
Description
「研究成果報告書概要(欧文)」より
Related Report
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