Extracellular matrix phenotype of rat mesangial cells in culture. Biosynthesis of collagen types I, III, IV, and V and a low molecular weight collagenous component and their regulation by dexamethasone

Abstract

Rat glomerular cells were cultured in vitro to evaluate their collagen phenotype. The enriched epithelial cell population that grew out from glomeruli in the initial stages of culture primarily synthesized type IV collagen. By 14 days, mesangial cell proliferation occurred with a coordinate change in collagen phenotype, after which time these cells mainly synthesized type I collagen and lesser amounts of types III, IV, and V collagens. In addition to the standard collagens, mesangial cells synthesized and accumulated in their extracellular matrix a small molecular weight collagenous protein that accounted for 16.6% of the total radioactivity incorporated into extracellular matrix proteins. This short-chain collagen, with an approximate molecular mass of 70,000 (70 kd), appears to be a unique product of mesangial cells. Collagen biosynthesis by the mesangial cells was down-regulated by dexamethasone in a time- and dose-dependent manner. Treatment with 10(-6) mol/L dexamethasone reduced synthesis of type I and type IV collagens by about 37% and 24%, respectively. Steady-state levels of the corresponding procollagen messenger RNAs were diminished in dexamethasone-treated mesangial cells. This effect of glucocorticoid was found to be specific because dexamethasone did not affect biosynthesis and secretion of noncollagenous proteins.