TRANSFORMING GROWTH FACTOR-BETA(1) ENHANCES GLOMERULAR COLLAGEN-SYNTHESIS IN DIABETIC RATS

In vitro glomerular collagen synthesis and its response to various con centrations of transforming growth factor-beta1 were studied in normal and diabetic rats. TGF-beta1 increased collagen synthesis in normal g lomeruli in a dose-dependent manner up to 5 ng/ml. Concentrations >5 n g/ml showed a gradual decline in collagen synthesis. Basal collagen sy nthesis was increased in diabetic glomeruli, but addition of TGF-beta1 had no effect. Antibody to TGF-beta1 prevented this increase in colla gen synthesis. Both circulating TGF-beta1 concentration and its glomer ular expression of mRNA were higher in diabetic than in normal rats. A lthough addition of TGF-beta1 did not increase synthesis in vitro, the absence of an effect is consistent with downregulation of its recepto rs attributable to the high circulating levels. This study clearly ind icates a regulatory role of TGF-beta1 in renal glomerular collagen syn thesis in the normal rat, and suggests a possible causal role for enha nced collagen synthesis in the diabetic rat.