1997 Fiscal Year Final Research Report Summary
The effect of mechanical stretch on TGF-beta and extracellular matrix expression in glomerular cells.
| Project/Area Number |
08671275
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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 | University of Tokyo |
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Principal Investigator |
KANAME Shinya University of Tokyo, School of Medicine (Branch Hospital) , The Fourth Department of Internal Medicine, Assistant Professor, 医学部・附属病院(分), 助手 (60224581)
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| Project Period (FY) |
1996 – 1997
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| Keywords | stretch / mesangial cells / TGF-beta / PDGF / glomerulosclerosis / glomerular hypertension / extracellular matrix |
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| Research Abstract |
We examined the effect of mechanical stretch on the expression of various growth factors and extracellular matrix(ECM)components in cultured glomerular mesangial cells. Mechanical stretch stimulated mRNA expression of TGF-beta1 and TGF-beta3 in a time- and elongation-dependent manner, and the cells secreted substantial amounts of TGF-beta proteins almost as a latent form, which was increased in response to stretch. Stretch also stimulated mRNA expression of collagen types I and IV,and fibronectin, major components of mesangial ECM.The stretch-induced ECM expression was largely mediated by autocrine/paracrine secretion of TGF-beta induced by stretch. Mechanical stretch also stimulated mRNA expression of all TGF-betaR isoforms, type I,II and III receptors and the binding of ^<125>I-labeled TGF-beta to each TGF-betaR isoform was actually increased by stretch. Mechanical stretch also stimulated mRNA expression of PDGF A- and B-chain. The stretch-induced mRNA expression of TGF-beta was inhibited by tyrosine kinase inhibitors. Moreover, the stretchinduced ECM and TGF-beta expression was both partially inhibited by anti-PDGF neutralizing antibody. These results show that mechanical stretch upregulates TGF-beta receptors and increases TGF-beta expression/secretion through tyrosine kinase-dependent mechanisms, which is enhanced by the stetch-induced PDGF,resulting in high levels of ECM expression after stretch in cultured mesangial cells. The results suggest that TGF-beta and PDGF may play an important role in the progression of glomerulosclerosis by glomerular hypertension in vivo.
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