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• W2064494420 abstract "Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by formation of cysts from tubular epithelial cells. Previous studies indicate that secretion of prostaglandin E 2 (PGE 2 ) into cyst fluid and production of cAMP underlie cyst expansion. However, the mechanism by which PGE 2 directly stimulates cAMP formation and modulates cystogenesis is still unclear, because the particular E-prostanoid (EP) receptor mediating the PGE 2 effect has not been characterized. Our goal is to define the PGE 2 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 2 induces cyst formation. Biochemical evidence gathered by using real-time RT-PCR mRNA analysis and immunodetection indicate the presence of EP 2 receptor in cystic epithelial cells in ADPKD kidney. Pharmacological evidence obtained by using PGE 2 -selective analogs further demonstrates that EP 2 mediates cAMP formation and cystogenesis. Functional evidence for a role of EP 2 receptor in mediating cAMP signaling was also provided by inhibiting EP 2 receptor expression with transfection of small interfering RNA in cystic epithelial cells. Our results indicate that PGE 2 produced in cyst fluid binds to adjacent EP 2 receptors located on the apical side of cysts and stimulates EP 2 receptor expression. PGE 2 binding to EP 2 receptor leads to cAMP signaling and cystogenesis by a mechanism that involves protection of cystic epithelial cells from apoptosis. The role of EP 2 receptor in mediating the PGE 2 effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease." @default.
• W2064494420 created "2016-06-24" @default.
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• W2064494420 date "2007-11-01" @default.
• W2064494420 modified "2023-10-01" @default.
• W2064494420 title "EP₂receptor mediates PGE₂-induced cystogenesis of human renal epithelial cells" @default.
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• W2064494420 doi "https://doi.org/10.1152/ajprenal.00036.2007" @default.
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