CHARACTERIZATION AND REGULATION OF THE LATENT TRANSFORMING GROWTH-FACTOR-BETA COMPLEX SECRETED BY VASCULAR PERICYTES

Transforming growth factor-beta (TGF-beta) stimulates the accumulation of extracellular matrix in renal and hepatic disease. Kidney glomerul ar mesangial cells (GMC) and liver fat-storing cells (FSC) produce lat ent or inactive TGF-beta. In this study, we characterized the latent T GF-beta complexes secreted by these cells. Human FSC produce a single latent TGF-beta complex, predominantly of the TGF-beta 1 isoform, wher eas GMC secrete multiple complexes of latent TGF-beta, containing beta 1 and beta 2 isoforms. At least four forms were identified in GMC usi ng ion exchange chromatography, including a peak not previously descri bed in other cell types which eluted at 0.12 M NaCl, and predominantly of the beta 2 isoform. Both cell types secrete the latent TGF-beta 1 binding protein of 190 kDa, as part of a high molecular weight TGF-bet a complex. Epidermal growth factor stimulates the secretion of latent TGF-beta and latent TGF-beta binding protein in both cell types. Secre tion of the latent TGF-beta in both cell types was found to be associa ted with secretion of decorin. This study shows that vascular pericyte s from the kidney and the liver have distinctly different profiles of latent TGF-beta complexes, with GMC secreting a unique form of latent TGF-beta 2. The regulatory effect of epidermal growth factor and plate let-derived growth factor has potential implication for the pathophysi ology of liver regeneration and chronic liver and kidney diseases. (C) 1996 Wiley-Liss, Inc.