{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:03:21Z","timestamp":1769115801803,"version":"3.49.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:p>Brain natriuretic peptide (BNP) produced by cardiac myocytes has antifibrotic and antigrowth properties and is a marker of cardiac hypertrophy. We previously showed that prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) is the main prostaglandin produced in myocytes treated with proinflammatory stimuli and stimulates protein synthesis by binding to its EP<jats:sub>4<\/jats:sub>receptor. We hypothesized that PGE<jats:sub>2<\/jats:sub>, acting through EP<jats:sub>4<\/jats:sub>, also regulates BNP gene expression. We transfected neonatal ventricular myocytes with a plasmid encoding the human BNP (hBNP) promoter driving expression of a luciferase reporter gene. PGE<jats:sub>2<\/jats:sub>increased hBNP promoter activity 3.5-fold. An EP<jats:sub>4<\/jats:sub>antagonist reduced the stimulatory effect of PGE<jats:sub>2<\/jats:sub>but not an EP<jats:sub>1<\/jats:sub>antagonist. Because EP<jats:sub>4<\/jats:sub>signaling can involve adenylate cyclase, cAMP, and protein kinase A (PKA), we tested the effect of H-89, a PKA inhibitor, on PGE<jats:sub>2<\/jats:sub>stimulation of the hBNP promoter. H-89 at 5 \u03bcM decreased PGE<jats:sub>2<\/jats:sub>stimulation of BNP promoter activity by 100%. Because p42\/44 MAPK mediates the effect of PGE<jats:sub>2<\/jats:sub>on protein synthesis, we also examined the role of MAPKs in the regulation of BNP promoter activity. PGE<jats:sub>2<\/jats:sub>stimulation of the hBNP promoter was inhibited by a MEK1\/2 inhibitor and a dominant-negative mutant of Raf, indicating that p42\/44 MAPK was involved. In contrast, neither a p38 MAPK inhibitor nor a JNK inhibitor reduced the stimulatory effect of PGE<jats:sub>2<\/jats:sub>. Involvement of small GTPases was also studied. Dominant-negative Rap inhibited PGE<jats:sub>2<\/jats:sub>stimulation of the hBNP promoter, but dominant-negative Ras did not. We concluded that PGE<jats:sub>2<\/jats:sub>stimulates the BNP promoter mainly via EP<jats:sub>4<\/jats:sub>, PKA, Rap, and p42\/44 MAPK.<\/jats:p>","DOI":"10.1152\/ajpheart.00904.2005","type":"journal-article","created":{"date-parts":[[2006,1,21]],"date-time":"2006-01-21T01:48:16Z","timestamp":1137808096000},"page":"H1740-H1746","source":"Crossref","is-referenced-by-count":28,"title":["PGE<sub>2<\/sub>stimulates human brain natriuretic peptide expression via EP<sub>4<\/sub>and p42\/44 MAPK"],"prefix":"10.1152","volume":"290","author":[{"given":"Jian-Yong","family":"Qian","sequence":"first","affiliation":[]},{"given":"Alicia","family":"Leung","sequence":"additional","affiliation":[]},{"given":"Pamela","family":"Harding","sequence":"additional","affiliation":[]},{"given":"Margot 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