Simonson M S, Herman W H, Dunn M J
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Adv Exp Med Biol. 1997;400A:279-86. doi: 10.1007/978-1-4615-5325-0_40.
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.
前列腺素诱导多种即早基因的表达，但这些反应背后的分子机制仍未得到充分表征。我们研究了前列腺素E2（PGE2）在系膜细胞中诱导原癌基因c-fos的表达，以此作为前列腺素调节基因的模型。PGE2诱导c-fos mRNA显著且短暂地积累。PGE2和血栓素A2（TxA2）对c-fos的诱导与磷脂酶C的诱导无关。添加外源性环磷酸腺苷（cAMP）未能诱导c-fos mRNA，这表明与腺苷酸环化酶相连的EP2受体的激活并不能解释PGE2对c-fos的诱导。这些数据与之前在NIH 3T3细胞中的实验结果形成对比，在NIH 3T3细胞中，PGE2通过cAMP依赖机制诱导c-fos。我们进一步表明，PGE2通过直接激活血清反应元件来诱导c-fos基因。综上所述，这些实验为一条将质膜上的PGE2受体与细胞核中的转录激活联系起来的途径提供了证据。
