{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:21:04Z","timestamp":1791174064770,"version":"4.1.0"},"reference-count":38,"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":1157,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["(#32003B-109906"],"award-info":[{"award-number":["(#32003B-109906"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Desir\u00e9e und Niels Yde foundation"},{"name":"Stiftung zur Krebsbek\u00e4mpfung"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Obstructive cholestasis induces liver injury, postoperative complications, and mortality after surgery. Adaptive control of cholestasis, including bile salt homeostasis, is necessary for recovery and survival. Peripheral serotonin is a cytoprotective neurotransmitter also associated with liver regeneration. The effect of serotonin on cholestatic liver injury is not known. Therefore, we tested whether serotonin affects the severity of cholestatic liver injury. We induced cholestasis by ligation of the bile duct (BDL) in either wild-type (WT) mice or mice lacking peripheral serotonin (<jats:italic toggle=\"yes\">Tph1<\/jats:italic>\n                                 <jats:sup>\u2212\/\u2212<\/jats:sup> and immune thrombocytopenic [ITP] mice). Liver injury was assessed by the levels of plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and tissue necrosis. Bile salt\u2013regulating genes were measured by quantitative polymerase chain reaction and confirmed by western blotting and immunohistochemistry. <jats:italic toggle=\"yes\">Tph1<\/jats:italic>\n                                 <jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed higher levels of plasma AST, ALT, bile salts, and hepatic necrosis after 3 days of BDL than WT mice. Likewise, liver injury was disproportional in ITP mice. Moreover, severe cholestatic complications and mortality after prolonged BDL were increased in <jats:italic toggle=\"yes\">Tph1<\/jats:italic>\n                                 <jats:sup>\u2212\/\u2212<\/jats:sup> mice. Despite the elevation in toxic bile salts, expression of genes involved in bile salt homeostasis and detoxification were not affected in <jats:italic toggle=\"yes\">Tph1<\/jats:italic>\n                                 <jats:sup>\u2212\/\u2212<\/jats:sup> livers. In contrast, the bile salt reabsorption transporters Ost\u03b1 and Ost\u03b2 were up-regulated in the kidneys of <jats:italic toggle=\"yes\">Tph1<\/jats:italic>\n                                 <jats:sup>\u2212\/\u2212<\/jats:sup> mice, along with a decrease in urinary bile salt excretion. Serotonin reloading of <jats:italic toggle=\"yes\">Tph1<\/jats:italic>\n                                 <jats:sup>\u2212\/\u2212<\/jats:sup> mice reversed this phenotype, resulting in a reduction of circulating bile salts and liver injury. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: We propose a physiological function of serotonin is to ameliorate liver injury and stabilize the bile salt pool through adaptation of renal transporters in cholestasis. (HEPATOLOGY 2012;56:209\u2013218)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.25626","type":"journal-article","created":{"date-parts":[[2012,1,30]],"date-time":"2012-01-30T16:02:00Z","timestamp":1327939320000},"page":"209-218","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":54,"title":["Serotonin protects mouse liver from cholestatic injury by decreasing bile salt pool after bile duct ligation"],"prefix":"10.1097","volume":"56","author":[{"given":"Jae-Hwi","family":"Jang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rickenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bostjan","family":"Humar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri Aristotle","family":"Raptis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuno","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Stieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Moritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Soll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panco","family":"Georgiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endre","family":"Laczko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Alain","family":"Clavien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-23-20241201","doi-asserted-by":"crossref","first-page":"49654966","DOI":"10.1073\/pnas.0801194105","article-title":"Deletion of the ileal basolateral bile acid transporter identifies the cellular sentinels that regulate the bile acid pool.","volume":"105","author":"Davis","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R2-23-20241201","doi-asserted-by":"crossref","first-page":"678693","DOI":"10.1038\/nrd2619","article-title":"Targeting bileacid signalling for metabolic diseases.","volume":"7","author":"Thomas","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"R3-23-20241201","doi-asserted-by":"crossref","first-page":"15781586","DOI":"10.1002\/hep.22196","article-title":"Loss of orphan receptor small heterodimer partner sensitizes mice to liver injury from obstructive cholestasis.","volume":"47","author":"Park","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R4-23-20241201","doi-asserted-by":"crossref","first-page":"422432","DOI":"10.1002\/hep.21494","article-title":"Activation of LXRs prevents bile acid toxicity and cholestasis in female mice.","volume":"45","author":"Uppal","year":"2007","journal-title":"HEPATOLOGY"},{"key":"R5-23-20241201","doi-asserted-by":"crossref","first-page":"318328","DOI":"10.1038\/ncpgasthep0521","article-title":"Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis.","volume":"3","author":"Beuers","year":"2006","journal-title":"Nat Clin Pract Gastroenterol Hepatol"},{"key":"R6-23-20241201","doi-asserted-by":"crossref","first-page":"267270","DOI":"10.1002\/bjs.1800710405","article-title":"Wound healing in obstructive jaundice.","volume":"71","author":"Armstrong","year":"1984","journal-title":"Br J Surg"},{"key":"R7-23-20241201","doi-asserted-by":"crossref","first-page":"271275","DOI":"10.1097\/00000658-198403000-00004","article-title":"Upper gastrointestinal bleeding. 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