{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:01:46Z","timestamp":1789599706833,"version":"build-2803163510"},"reference-count":48,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2012,11,15]]},"abstract":"<jats:p>\n                    Prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) contributes to cystogenesis in genetically nonorthologous models of autosomal dominant polycystic kidney disease (ADPKD). However, it remains unknown whether PGE\n                    <jats:sub>2<\/jats:sub>\n                    induces the classic features of cystic epithelia in genetically orthologous models of ADPKD. We hypothesized that, in ADPKD epithelia, PGE\n                    <jats:sub>2<\/jats:sub>\n                    induces proliferation and chloride (Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) secretion, two archetypal phenotypic features of ADPKD. To test this hypothesis, proliferation and Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion were measured in renal epithelial cells deficient in polycystin-1 (PC-1). PC-1-deficient cells increased in cell number (proliferated) faster than PC-1-replete cells, and this proliferative advantage was abrogated by cyclooxygenase inhibition, indicating a role for PGE\n                    <jats:sub>2<\/jats:sub>\n                    in cell proliferation. Exogenous administration of PGE\n                    <jats:sub>2<\/jats:sub>\n                    increased proliferation of PC-1-deficient cells by 38.8 \u00b1 5.2% ( P &lt; 0.05) but inhibited the growth of PC-1-replete control cells by 49.4 \u00b1 1.9% ( P &lt; 0.05). Next, we tested whether PGE\n                    <jats:sub>2<\/jats:sub>\n                    -specific E prostanoid (EP) receptor agonists induce intracellular cAMP and downstream \u03b2-catenin activation. PGE\n                    <jats:sub>2<\/jats:sub>\n                    and EP4 receptor agonism (TCS 2510) increased intracellular cAMP concentration and the abundance of active \u03b2-catenin in PC-1-deficient cells, suggesting a mechanism for PGE\n                    <jats:sub>2<\/jats:sub>\n                    -mediated proliferation. Consistent with this hypothesis, antagonizing EP4 receptors reverted the growth advantage of PC-1-deficient cells, implicating a central role for the EP4 receptor in proliferation. To test whether PGE\n                    <jats:sub>2<\/jats:sub>\n                    -dependent Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion is also enhanced in PC-1-deficient cells, we used an Ussing chamber to measure short-circuit current ( I\n                    <jats:sub>sc<\/jats:sub>\n                    ). Addition of PGE\n                    <jats:sub>2<\/jats:sub>\n                    induced a fivefold higher increase in I\n                    <jats:sub>sc<\/jats:sub>\n                    in PC-1-deficient cells compared with PC-1-replete cells. This PGE\n                    <jats:sub>2<\/jats:sub>\n                    -induced increase in I\n                    <jats:sub>sc<\/jats:sub>\n                    in PC-1-deficient cells was blocked by CFTR-172 and flufenamic acid, indicating that PGE\n                    <jats:sub>2<\/jats:sub>\n                    activates CFTR and calcium-activated Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels. In conclusion, PGE\n                    <jats:sub>2<\/jats:sub>\n                    activates aberrant signaling pathways in PC-1-deficient epithelia that contribute to the proliferative and secretory phenotype characteristic of ADPKD and suggests a therapeutic role for PGE\n                    <jats:sub>2<\/jats:sub>\n                    inhibition and EP4 receptor antagonism.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00010.2012","type":"journal-article","created":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T21:08:24Z","timestamp":1346274504000},"page":"F1425-F1434","source":"Crossref","is-referenced-by-count":27,"title":["Prostaglandin E\n                    <sub>2<\/sub>\n                    mediates proliferation and chloride secretion in ADPKD cystic renal epithelia"],"prefix":"10.1152","volume":"303","author":[{"given":"Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medicine, The Mount Sinai School of Medicine, New York, New York;"},{"name":"Department of Medicine, The James J. Peters Veterans Affairs Medical Center, Bronx, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumitha","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai School of Medicine, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Battini","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai School of Medicine, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai School of Medicine, New York, New York;"},{"name":"Department of Medicine, The James J. 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