Endothelin stimulates prostaglandin endoperoxide synthase-2 mRNA expression and protein synthesis through a tyrosine kinase-signaling pathway in rat mesangial cells

Abstract

We evaluated the role of endothelin-1 (ET-1), a vasoconstrictor peptide, to regulate prostaglandin endoperoxide synthase (PGHS)-1 and -2 gene expression and protein synthesis in cultured rat mesangial cells (MC). ET-1 induced mRNA for PGHS-2 but not PGHS-1 and also stimulated protein accumulation of PGHS-2 but not PGHS-1 in MC. ET-1 induction of PGHS-2 protein was accompanied by a sustained enhancement of enzymatic activity assessed by conversion of arachidonic acid to prostaglandin E2. The ET-1-stimulated PGHS-2 expression was reduced with protein tyrosine kinase but not with protein kinase C inhibitors or in protein kinase C-depleted cells. Both dexamethasone and heparin reduced ET-1-activated PGHS-2 mRNA expression and protein formation. We conclude that in MC, ET-1 induces PGHS-2 through a protein tyrosine kinase-dependent pathway.