Characterization and regulation of the latent transforming growth factor-β complex secreted by vascular pericytes

Abstract

Transforming growth factor-beta (TGF-beta) stimulates the accumulation of extracellular matrix in renal and hepatic disease. Kidney glomerular mesangial cells (GMC) and liver fat-storing cells (FSC) produce latent of inactive TGF-beta. In this study, we characterized the latent TGF-beta complexes secreted by these cells. Human FSC produce a single latent TGF-beta complex, predominantly of the TGF-beta 1 isoform, whereas GMC secrete multiple complexes of latent TGF-beta, containing beta 1 and beta 2 isoforms. At least four forms were identified in GMC using ion exchange chromatography, including a peak not previously described 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-beta complex. Epidermal growth factor stimulates the secretion of latent TGF-beta and latent TGF-beta binding protein in both cell types. Secretion of latent TGF-beta in both cell types was found to be associated with secretion of decorin. This study shows that vascular pericytes 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 platelet-derived growth factor has potential implication for the pathophysiology of liver regeneration and chronic liver and kidney diseases.