| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
TGF-beta1 has been shown to play an important role in maintaining the renal histological structure as well as the glomerular and tubular functions. TGF-beta1 is usually secreted by normal cells in a biologically inactive or latent form with a high molecular weight. The latent form of TGF-beta1 may have two different structures of large latent TGF-beta1 with LTBP and small latent TGF-beta1 without LTBP.LTBP plays a central role in the assembly, secretion, activation and localization of TGF-beta1. In the present study, we investigated which renal cells produce large or small latent TGF-beta1 and also tried to determine the precise localization of TGF-beta1 protein in the kidney of normal rats or adriamycin-induced FGS model rats, using RT-PCR,in situ hybridization and immunohistochemistory. In the normal kidney. TGF-beta1 mRNA was detected in all nephron segments and glomeruli. On the other hand, LTBP mRNA was present only in the glomeruli, while it was absent in every segment of the renal tubules. This finding suggested that the tubular cells secrete small latent TGF-beta1, while glomerular cells secrete large latent TGF-beta1. In the diseased kidney, a TGF-beta bioassay revealed a progressive increase in latent TGF-beta1 secretion from cultured renal tissues. The tubular cells also began to secrete large latent TGF-beta1, which closely paralleled the degree of the tubulointerstitial changes. The increased amount of large latent TGF-beta was localized in the sclerotic and fibrotic tissue in association with the extracellular matrix (ECM). In conclusion, the tubular cells might thus turn out to be a source of large latent TGF-beta1 in progressive process of this model, while matrix-associated large latent TGF-beta1 may play an important role in the ECM metabolism of either sclerotic or fibrotic lesions.
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