{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:43:40Z","timestamp":1791297820914,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2069,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,1]]},"abstract":"\n \n \n Organic solute transporter alpha-beta (Ost\u03b1-Ost\u03b2) is a heteromeric bile acid and sterol transporter that facilitates the enterohepatic and renal-hepatic circulation of bile acids. Hepatic expression of this basolateral membrane protein is increased in cholestasis, presumably to facilitate removal of toxic bile acids from the liver. In this study, we show that the cholestatic phenotype induced by common bile duct ligation (BDL) is reduced in mice genetically deficient in<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1. Although<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1\u2212\/\u2212 mice have a smaller bile acid pool size, which could explain lower serum and hepatic levels of bile acids after BDL, gallbladder bilirubin and urinary bile acid concentrations were significantly greater in<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1\u2212\/\u2212 BDL mice, suggesting additional alternative adaptive responses. Livers of<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1\u2212\/\u2212 mice had higher messenger RNA levels of constitutive androstane receptor (Car) than wild-type BDL mice and increased expression of Phase I enzymes (<\/jats:bold>\n \n Cyp7a1\n <\/jats:bold>\n ,<\/jats:bold>\n \n Cyp2b10\n <\/jats:bold>\n ,<\/jats:bold>\n \n Cyp3a11\n <\/jats:bold>\n ), Phase II enzymes (<\/jats:bold>\n \n Sult2a1\n <\/jats:bold>\n ,<\/jats:bold>\n \n Ugt1a1\n <\/jats:bold>\n ), and Phase III transporters (<\/jats:bold>\n \n Mrp2\n <\/jats:bold>\n ,<\/jats:bold>\n \n Mrp3\n <\/jats:bold>\n ). Following BDL, the bile acid pool size increased in<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1\u2212\/\u2212 mice and protein levels for the hepatic basolateral membrane export transporters, multidrug resistance-associated protein 3 (Mrp3) and Mrp4, and for the apical bilirubin transporter, Mrp2, were all increased. In the kidney of<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1\u2212\/\u2212 mice after BDL, the apical bile acid uptake transporter Asbt is further reduced, whereas the apical export transporters Mrp2 and Mrp4 are increased, resulting in a significant increase in urinary bile acid excretion.<\/jats:bold>\n \n Conclusion:\n <\/jats:bold>\n These findings indicate that loss of<\/jats:bold>\n \n Ost\n <\/jats:bold>\n \u03b1 provides protection from liver injury in obstructive cholestasis through adaptive responses in both the kidney and liver that enhance clearance of bile acids into urine and through detoxification pathways most likely mediated by the nuclear receptor Car. (Hepatology 2010.)<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.23265","type":"journal-article","created":{"date-parts":[[2009,9,4]],"date-time":"2009-09-04T13:01:02Z","timestamp":1252069262000},"page":"181-190","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":70,"title":["Mouse Organic Solute Transporter \u03b1 Deficiency Enhances Renal Excretion of Bile Acids and Attenuates Cholestasis"],"prefix":"10.1097","volume":"51","author":[{"given":"Carol J.","family":"Soroka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Mennone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee R.","family":"Hagey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazzareno","family":"Ballatori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-23-20241201","doi-asserted-by":"crossref","first-page":"G179","DOI":"10.1152\/ajpgi.90319.2008","article-title":"OstOst is required for bile acid and conjugated steroid disposition in the intestine, kidney, and liver.","volume":"295","author":"Ballatori","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R2-23-20241201","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1073\/pnas.0712328105","article-title":"The organic solute transporter , OstOst, is essential for intestinal bile acid transport and homeostasis.","volume":"105","author":"Rao","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R3-23-20241201","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/hep.20961","article-title":"OSTOST: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia.","volume":"42","author":"Ballatori","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R4-23-20241201","doi-asserted-by":"crossref","first-page":"6960","DOI":"10.1074\/jbc.M412752200","article-title":"The heteromeric organic solute transporter alphabeta, OstOst, is an ileal basolateral bile acid transporter.","volume":"280","author":"Dawson","year":"2005","journal-title":"J Biol Chem"},{"key":"R5-23-20241201","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2005.09.001","article-title":"Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid 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