Basic fibroblast growth factor stimulates glomerular mesangial cell proliferation through a protein kinase C-independent pathway.
Basic Fibroblast Growth Factor (bFGF) is shown to be a potent mitogen for cultured glomerular mesangial cells. bFGF induces an increase in cell number and stimulates DNA synthesis measured by [3H]thymidine incorporation in normal as well as in protein kinase C-depleted cells. The ED50 observed in both cases are nearly identical (approximately 0.04 nM) and maximal responses are obtained at 1 nM. Staurosporine, a potent protein kinase C inhibitor, does not prevent bFGF from inducing mitogenesis. On the contrary, the tumour promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) and the bradykinin derivative Des-Arg9bradykinin that we have previously shown as mitogens for mesangial cells, fail to trigger DNA synthesis or cell proliferation upon staurosporine treatment or in protein kinase C-depleted cells. bFGF is unable to induce the association of the enzyme to membranes, the so-called translocation process, although the growth factor induces a slight production of diacylglycerol. Using a highly resolutive two-dimensional electrophoresis, we show that bFGF, in contrast to TPA, is unable to stimulate the phosphorylation of a Mr 80,000/pI 4.5 protein, a major and specific protein kinase C substrate. By contrast, bFGF stimulates the phosphorylation of a Mr 28,000/pI 5.7-5.9 protein in normal as well as in protein kinase C-depleted cells while TPA induces this protein phosphorylation only in normal cells. Our results suggest that bFGF exerts its proliferative action on mesangial cells through a protein kinase C-independent pathway and that the growth factor does not activate anyway the enzyme in this cell type.
Issandou
M
M
INSERM U133, Faculté de Médecine, Toulouse, France.
Darbon
J M
JM
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate