PI-3-kinase and MAPK regulate mesangial cell proliferation and migration in response to PDGF
Abstract
Proliferation and migration are important biological responses of mesangial cells to injury. Platelet-derived growth factor (PDGF) is a prime candidate to mediate these responses in glomerular disease. PDGF and its receptor (PDGFR) are upregulated in the mesangium during glomerular injury. We have recently shown that PDGF activates phosphatidylinositol 3-kinase (PI-3-kinase) in cultured mesangial cells. The role of this enzyme and other more distal signaling pathways in regulating migration and proliferation of mesangial cells has not yet been addressed. In this study, we used two inhibitors of PI-3-kinase, wortmannin (WMN) and LY-294002, to investigate the role of this enzyme in these processes. Pretreatment of mesangial cells with WMN and LY-294002 dose-dependently inhibited PDGF-induced PI-3-kinase activity assayed in antiphosphotyrosine immunoprecipitates. WMN pretreatment also inhibited the PI-3-kinase activity associated with anti-PDGFR beta immunoprecipitates prepared from mesangial cells treated with PDGF. Pretreatment of the cells with different concentrations of WMN resulted in a dose-dependent inhibition of PDGF-induced DNA synthesis. Both WMN and LY-294002 inhibited PDGF-stimulated migration of mesangial cells in a ...Continue Reading
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