HIV-1 gp120 envelope protein modulates proliferation of human glomerular epithelial cells

Glomerular epithelial cells (CEC) have been demonstrated to undergo morphol ogical alterations in human immunodeficiency virus (HIV)-associated focal g lomerulosclerosis. In the present study, we evaluated the effect of HIV-1 g p120 envelope protein on the growth of cultured human (H) GEC. gp120 protei n enhanced (P < 0.001) the proliferation of HGEC at lower concentrations. T he mitogenic effect of gp120 protein on HGEC was further confirmed by enhan ced accumulation of proliferating nuclear cell antigen (PCNA) by gp120 prot ein-treated cells, as compared with control cells. On the contrary, gp120 p rotein at higher concentrations suppressed (P < 0.001) the growth of HGEC. To evaluate the mechanism of gp120 protein-induced HGEC growth suppression, we examined the effect of gp120 protein on HGEC apoptosis. gp120 protein a t higher concentrations promoted the apoptosis of HGEC. At higher concentra tions, gp120 protein also enhanced DNA fragmentation of HGEC. Anti-gp120 an tibody attenuated the proliferative as well as the apoptotic effects of gp1 20 protein on HGEC. Because protein kinase C as well as tyrosine kinase inh ibitors partially inhibited gp120-induced proliferation, gp120 appears to b e activating both the protein kinase C and tyrosine kinase pathways. In add ition, gp120 protein at lower concentrations enhanced mRNA expression of c- fos and at higher concentrations promoted mRNA expression of c-jun. We conc lude that gp120 has a bimodal effect on proliferation of HGEC. This effect may be mediated through the activation of early growth genes. J. Cell. Bioc hem. 76:61-70, 1999. (C) 1999 Wiley-Liss, Inc.