Distinct signaling pathways mediate induction of c-fos by PGE2 in glomerular mesangial cells.

Prostanoids induce expression of several immediate-early genes but the molecular mechanisms underlying these responses remain poorly characterized. We have studied induction of the proto-oncogenc c-fos by PGE2 in mesangial cells as a model of gene regulation by prostanoids. PGE2 induced marked and transient accumulation of c-fos mRNA. Induction of c-fos by PGE2 and TxA2 did not correlate with induction of phospholipase C. Addition of exogenous cAMP failed to induce c-fos mRNA, suggesting that activation of an EP2 receptor linked to adenylate cyclase did not account for induction of c-fos by PGE2. These data contrast with previous experiments in NIH 3T3 cells where PGE2 induced c-fos by a cAMP-dependent mechanism. We further showed that PGE2 induces the c-fos gene by direct activation of the serum response element. Taken together these experiments provide evidence for a pathway linking a PGE2 receptor on the plasma membrane to transcriptional activation in the nucleus.