{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:36:30Z","timestamp":1790285790103,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,11]]},"abstract":"\n Background<\/jats:title>\n The bile acid-activated receptors, including the membrane G protein\u2013coupled receptor TGR5 and nuclear farnesoid X receptor (FXR), have roles in kidney diseases. In this study, we investigated the role of TGR5 in renal water handling and the underlying molecular mechanisms.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We used tubule suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys to investigate the effect of TGR5 signaling on aquaporin-2 (AQP2) expression, and examined the\n in vivo<\/jats:italic>\n effects of TGR5 in mice with lithium-induced nephrogenic diabetes insipidus (NDI) and\n Tgr5<\/jats:italic>\n knockout (\n Tgr5<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ) mice.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Activation of TGR5 by lithocholic acid (LCA), an endogenous TGR5 ligand, or INT-777, a synthetic TGR5-specific agonist, induced AQP2 expression and intracellular trafficking in rat IMCD cells\n via<\/jats:italic>\n a cAMP-protein kinase A signaling pathway. In mice with NDI, dietary supplementation with LCA markedly decreased urine output and increased urine osmolality, which was associated with significantly upregulated AQP2 expression in the kidney inner medulla. Supplementation with endogenous FXR agonist had no effect. In primary IMCD suspensions from lithium-treated rats, treatment with INT-767 (FXR and TGR5 dual agonist) or INT-777, but not INT-747 (FXR agonist), increased AQP2 expression.\n Tgr5<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice exhibited an attenuated ability to concentrate urine in response to dehydration, which was associated with decreased AQP2 expression in the kidney inner medulla. In lithium-treated\n Tgr5<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice, LCA treatment failed to prevent reduction of AQP2 expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n TGR5 stimulation increases renal AQP2 expression and improves impaired urinary concentration in lithium-induced NDI. TGR5 is thus involved in regulating water metabolism in the kidney.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018030271","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T12:33:26Z","timestamp":1539174806000},"page":"2658-2670","source":"Crossref","is-referenced-by-count":56,"title":["Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2\u2013Mediated Water Homeostasis"],"prefix":"10.1681","volume":"29","author":[{"given":"Suchun","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaojuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglun","family":"Kong","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoduo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Jung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Reich","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital D\u00fcsseldorf, Medical Faculty at Heinrich-Heine-University, D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brady H.","family":"Bunkelman","sequence":"additional","affiliation":[{"name":"Department of Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi Z.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and"},{"name":"Division of Kidney Urologic Pathology, Johns Hopkins University, Baltimore, Maryland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Keitel","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital D\u00fcsseldorf, Medical Faculty at Heinrich-Heine-University, D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Hwan","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell 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