{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:02:29Z","timestamp":1789491749183,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Background:<\/jats:title>\n \n Renal sodium retention is a central driver of hypertension and fluid overload. Prostaglandin E\n 2<\/jats:sub>\n (PGE\n 2<\/jats:sub>\n ) has long been identified as a potent natriuretic and diuretic factor. However, the mechanisms governing intrarenal PGE\n 2<\/jats:sub>\n signaling and tubular sodium transport remain incompletely understood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Global and renal tubule-specific\n Slco4a1<\/jats:italic>\n knockout mouse, as well as renal tubule-specific\n Slco4a1<\/jats:italic>\n overexpressing mice, were generated to investigate the role of SLCO4A1 in renal sodium and water homeostasis. Computational docking, cellular studies, and in vivo functional analyses were performed to evaluate the role of SLCO4A1in intrarenal distribution of PGE\n 2<\/jats:sub>\n and its impact on tubular sodium transport.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n SLCO4A1 was predominantly localized to the basolateral membrane of multiple renal tubular epithelial cells. Global and renal tubule-specific\n Slco4a1<\/jats:italic>\n gene deletion increased urine output and sodium excretion and reduced sodium reabsorption across multiple nephron segments in mice. This was accompanied by downregulation of key sodium transporters and channels including SGLT2, NHE3, NKCC2, NCC and ENaC. In contrast, renal tubule-specific overexpression of\n Slco4a1<\/jats:italic>\n displayed an opposite effect. Mechanistically,\n Slco4a1<\/jats:italic>\n deficiency led to accumulation of PGE\n 2<\/jats:sub>\n in the kidney interstitum, which suppressed the expression of sodium transporter and channels via the EP receptors. Specifically, EP\n 1<\/jats:sub>\n mediated the PGE\n 2<\/jats:sub>\n -induced suppression of NKCC2, \u03b1-ENaC, and \u03b2-ENaC. EP\n 2<\/jats:sub>\n was responsible for the suppression of NCC, while EP\n 3<\/jats:sub>\n was involved in suppressing SGLT2, NHE3 and \u03b3-ENaC.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Collectively, these findings uncovered a previously unrecognized role of SLCO4A1 in regulating intrarenal PGE\n 2<\/jats:sub>\n distribution and identified SLCO4A1-PGE\n 2<\/jats:sub>\n -EP receptor axis in fine-tuning renal tubular sodium transport.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001258","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:05:10Z","timestamp":1789488310000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["SLCO4A1 Governs PGE2-Mediated Natriuresis in the Kidney"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-3954","authenticated-orcid":false,"given":"Yanlin","family":"Guo","sequence":"first","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Ma","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-4663","authenticated-orcid":false,"given":"Chunxiu","family":"Du","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Lin","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9197-8922","authenticated-orcid":false,"given":"Caichao","family":"Ye","sequence":"additional","affiliation":[{"name":"Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taotao","family":"Luo","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaifang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifen","family":"Li","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowan","family":"Sun","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhi","family":"Huang","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ye","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-0932","authenticated-orcid":false,"given":"Hu","family":"Xu","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6370-1865","authenticated-orcid":false,"given":"Lihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-9919","authenticated-orcid":false,"given":"Yulong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5231-0209","authenticated-orcid":false,"given":"Youfei","family":"Guan","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China"},{"name":"Key Laboratory of Cellular Physiology of the Ministry of Education of China, Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-2423","authenticated-orcid":false,"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"},{"name":"Kidney Health Institute, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,9,15]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:05:10Z","timestamp":1789488310000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001258","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"assertion":[{"value":"2026-05-16","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}