Transforming growth factor-beta 1 enhances glomerular collagen synthesis in diabetic rats

In vitro glomerular collagen synthesis and its response to various concentrations of transforming growth factor-beta 1 were studied in normal and diabetic rats. TGF-beta 1 increased collagen synthesis in normal glomeruli in a dose-dependent manner up to 5 ng/ml. Concentrations > 5 ng/ml showed a gradual decline in collagen synthesis. Basal collagen synthesis was increased in diabetic glomeruli, but addition of TGF-beta 1 had no effect. Antibody to TGF-beta 1 prevented this increase in collagen synthesis. Both circulating TGF-beta 1 concentration and its glomerular expression of mRNA were higher in diabetic than in normal rats. Although addition of TGF-beta 1 did not increase synthesis in vitro, the absence of an effect is consistent with downregulation of its receptors attributable to the high circulating levels. This study clearly indicates a regulatory role of TGF-beta 1 in renal glomerular collagen synthesis in the normal rat, and suggests a possible causal role for enhanced collagen synthesis in the diabetic rat.