{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:51:54Z","timestamp":1787241114075,"version":"build-2736575974"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T00:00:00Z","timestamp":1463529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T00:00:00Z","timestamp":1463529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>\n                    The adenoviral gene transfer of human aquaporin\u20101 (hAQP1) water channels to the liver of 17\u03b1\u2010ethinylestradiol\u2010induced cholestatic rats improves bile flow, in part by enhancing canalicular hAQP1\u2010mediated osmotic water secretion. To gain insight into the mechanisms of 17\u03b1\u2010ethinylestradiol cholestasis improvement, we studied the biliary output of bile salts (BS) and the functional expression of the canalicular BS export pump (BSEP; ABCB11). Adenovector encoding hAQP1 (AdhAQP1) or control vector was administered by retrograde intrabiliary infusion. AdhAQP1\u2010transduced cholestatic rats increased the biliary output of major endogenous BS (50%\u201080%,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05) as well as that of taurocholate administered in choleretic or trace radiolabel amounts (around 60%,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05). Moreover, liver transduction with AdhAQP1 normalized serum BS levels, otherwise markedly elevated in cholestatic animals. AdhAQP1 treatment was unable to improve BSEP protein expression in cholestasis; however, its transport activity, assessed by adenosine triphosphate\u2010dependent taurocholate transport in canalicular membrane vesicles, was induced by 90% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05). AdhAQP1 administration in noncholestatic rats induced no significant changes in either biliary BS output or BSEP activity. Canalicular BSEP, mostly present in raft (high cholesterol) microdomains in control rats, was largely found in nonraft (low cholesterol) microdomains in cholestasis. Considering that BSEP activity directly depends on canalicular membrane cholesterol content, decreased BSEP presence in rafts may contribute to BSEP activity decline in 17\u03b1\u2010ethinylestradiol cholestasis. In AdhAQP1\u2010transduced cholestatic rats, BSEP showed a canalicular microdomain distribution similar to that of control rats, which provides an explanation for the improved BSEP activity.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Hepatocyte canalicular expression of hAQP1 through adenoviral gene transfer promotes biliary BS output by modulating BSEP activity in estrogen\u2010induced cholestasis, a novel finding that might help us to better understand and treat cholestatic disorders. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;64:535\u2010548)\n                  <\/jats:p>","DOI":"10.1002\/hep.28564","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T01:34:49Z","timestamp":1458610489000},"page":"535-548","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["Hepatic gene transfer of human aquaporin\u20101 improves bile salt secretory failure in rats with estrogen\u2010induced cholestasis"],"prefix":"10.1097","volume":"64","author":[{"given":"Julieta","family":"Marrone","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental,Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET),Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas,Universidad Nacional de Rosario,Rosario,Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro R.","family":"Soria","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental,Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET),Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas,Universidad Nacional de Rosario,Rosario,Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Danielli","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental,Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET),Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas,Universidad Nacional de Rosario,Rosario,Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo L.","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental,Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET),Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas,Universidad Nacional de Rosario,Rosario,Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cecilia","family":"Larocca","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental,Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET),Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas,Universidad Nacional de Rosario,Rosario,Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal A.","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental,Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET),Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas,Universidad Nacional de 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