Factors involved in the regulation of mesangial cell proliferation in vitro and in vivo.

One of the central features of many human glomerular diseases is the proliferation of the smooth muscle cell-like mesangial cells. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. To investigate the regulation of mesangial cell proliferation in vivo we have studied the mesangioproliferative glomerulonephritis that is induced by injection of antibody directed against the Thy 1.1 antigen on the mesangial cell surface in rats. In this review, we discuss the role of three cytokines in the mesangioproliferative response, namely platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokines are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to exert both paracrine and autocrine regulatory functions on mesangial cells. In vivo studies show that PDGF, bFGF and TGF-beta participate in either the mesangial cell proliferation or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody. Based on currently available data we propose that bFGF may participate in the initiation, PDGF in the maintenance, and TGF-beta in the resolution of mesangial cell proliferation in vivo. Further analysis of the mitogens operative in vivo may ultimately result in the design of new therapeutic strategies to treat progressive glomerular mesangioproliferative diseases.