{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:59:55Z","timestamp":1790438395083,"version":"4.1.0"},"reference-count":56,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p>Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by formation of cysts from tubular epithelial cells. Previous studies indicate that secretion of prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) into cyst fluid and production of cAMP underlie cyst expansion. However, the mechanism by which PGE<jats:sub>2<\/jats:sub>directly stimulates cAMP formation and modulates cystogenesis is still unclear, because the particular E-prostanoid (EP) receptor mediating the PGE<jats:sub>2<\/jats:sub>effect has not been characterized. Our goal is to define the PGE<jats:sub>2<\/jats:sub>receptor subtype involved in ADPKD. We used a three-dimensional cell-culture system of human epithelial cells from normal and ADPKD kidneys in primary cultures to demonstrate that PGE<jats:sub>2<\/jats:sub>induces cyst formation. Biochemical evidence gathered by using real-time RT-PCR mRNA analysis and immunodetection indicate the presence of EP<jats:sub>2<\/jats:sub>receptor in cystic epithelial cells in ADPKD kidney. Pharmacological evidence obtained by using PGE<jats:sub>2<\/jats:sub>-selective analogs further demonstrates that EP<jats:sub>2<\/jats:sub>mediates cAMP formation and cystogenesis. Functional evidence for a role of EP<jats:sub>2<\/jats:sub>receptor in mediating cAMP signaling was also provided by inhibiting EP<jats:sub>2<\/jats:sub>receptor expression with transfection of small interfering RNA in cystic epithelial cells. Our results indicate that PGE<jats:sub>2<\/jats:sub>produced in cyst fluid binds to adjacent EP<jats:sub>2<\/jats:sub>receptors located on the apical side of cysts and stimulates EP<jats:sub>2<\/jats:sub>receptor expression. PGE<jats:sub>2<\/jats:sub>binding to EP<jats:sub>2<\/jats:sub>receptor leads to cAMP signaling and cystogenesis by a mechanism that involves protection of cystic epithelial cells from apoptosis. The role of EP<jats:sub>2<\/jats:sub>receptor in mediating the PGE<jats:sub>2<\/jats:sub>effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease.<\/jats:p>","DOI":"10.1152\/ajprenal.00036.2007","type":"journal-article","created":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T00:59:32Z","timestamp":1188435572000},"page":"F1622-F1632","source":"Crossref","is-referenced-by-count":42,"title":["EP<sub>2<\/sub>receptor mediates PGE<sub>2<\/sub>-induced cystogenesis of human renal epithelial cells"],"prefix":"10.1152","volume":"293","author":[{"given":"Gerard","family":"Elberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Elberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa 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