| Project/Area Number |
08671289
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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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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Growth factor / TGF-beta / Soluble receptor / Glomerulosclerosis / Renal fibrosis / matrix / TGF-beta localization / TGF-beta acctivation / 糸球体疾患 / マトリックス / TGF-βレセプター / LTBP / アデノウイルス / 遺伝子導入 |
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| Research Abstract |
1.The latency of TGF-beta and chronicity of renal diseases
Our previous studies demonstrated that in a chronic renal disease model, most of TGF-beta is not activated and exsits as a latent form in tissue. The tissue storage of latent TGF-beta may be important for chronicity of histological changes. Tissue localization of latent TGF-beta was examined in vitro and in vivo. The matrices from mesangial cell cultures were shown to contain a large amount of latent TGF-beta. In an experimental FGS model, latent TGF-beta accumulates in the sclerosing glomeruli and the fibrous interstitium extensively and coexists with the other matrix proteins. The matrix-associated latent TGF-beta may serve as a chronic stimulus driving new ECM synthesis, which is important for both keeping and developing sclerosis or fibrotic tissues.
2.The effect of TGF-beta soluble receptor on renal fibrosis
The TGF-beta soluble receptor, which is extracellular domain of TGF-beta type 2 receptor has been expected to inhibit TGF-beta action in renal diseases. The gene of the soluble receptor was transfectd to muscle in rats with unilateral ureter obstruction, using adenovirus vectors. The interstitial fibrosis was attenuated in association with the increased serum levels of the soluble receptor. TGF-beta soluble receptor is a potent inhibitor of TGF-beta to modulate renal histological lesions.
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