PGE2 induces c-fos expression by a cAMP-independent mechanism in glomerular mesangial cells

Experimental Cell Research
M S SimonsonMichael J. Dunn

Abstract

Prostanoids induce expression of several immediate-early genes, but the molecular mechanisms underlying these responses remain poorly characterized. We studied induction of the proto-oncogene 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. Addition of exogenous 8-bromo-cAMP or forskolin 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 in which PGE2 induced c-fos by a cAMP-dependent mechanism. Depletion of protein kinase C blocked induction of c-fos mRNA by PGE2, whereas a protein tyrosine kinase inhibitor had no effect. We further showed that PGE2 induces the c-fos gene by increasing the transactivating capacity of the serum-response element. Transient transfections with a CAT fusion gene driven by an AP-1 cis-element demonstrated that although PGE2 markedly induced c-fos, PGE2 did not increase AP-1-driven transcriptional responses. Electrophoretic gel mobility shift assays revealed that PGE2 failed to increase binding of AP-1 complexes to a consensus AP-1 DNA sequence. Take...Continue Reading

Citations

Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·G LiuZ Dong
Jan 16, 1998·Prostaglandins, Leukotrienes, and Essential Fatty Acids·A SellmayerP C Weber
Jan 30, 2014·The Journal of Clinical Endocrinology and Metabolism·A Hari KishoreR Ann Word
May 21, 1999·The Journal of Biological Chemistry·M BhattacharyaS Chemtob
May 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·H IwahashiS Hanazawa
Mar 4, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J Fitzgerald, M Hughes-Fulford
Dec 9, 1998·The American Journal of Physiology·I DumontS Chemtob

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