{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:17:13Z","timestamp":1790752633496,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur, de la Recherche et de l\u2019Innovation"},{"name":"FILFOIE (Paris, France)"},{"name":"AMFE (\u201cAssociation Maladie Foie Enfants\u201d, Malakoff, France)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ABCB11 is responsible for biliary bile acid secretion at the canalicular membrane of hepatocytes. Variations in the ABCB11 gene cause a spectrum of rare liver diseases. The most severe form is progressive familial intrahepatic cholestasis type 2 (PFIC2). Current medical treatments have limited efficacy. Here, we report the in vitro study of Abcb11 missense variants identified in PFIC2 patients and their functional rescue using cystic fibrosis transmembrane conductance regulator potentiators. Three ABCB11 disease-causing variations identified in PFIC2 patients (i.e., A257V, T463I and G562D) were reproduced in a plasmid encoding an Abcb11-green fluorescent protein. After transfection, the expression and localization of the variants were studied in HepG2 cells. Taurocholate transport activity and the effect of potentiators were studied in Madin\u2013Darby canine kidney (MDCK) clones coexpressing Abcb11 and the sodium taurocholate cotransporting polypeptide (Ntcp\/Slc10A1). As predicted using three-dimensional structure analysis, the three variants were expressed at the canalicular membrane but showed a defective function. Ivacaftor, GLP1837, SBC040 and SBC219 potentiators increased the bile acid transport of A257V and T463I and to a lesser extent, of G562D Abcb11 missense variants. In addition, a synergic effect was observed when ivacaftor was combined with SBC040 or SBC219. Such potentiators could represent new pharmacological approaches for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the function of the transporter.<\/jats:p>","DOI":"10.3390\/ijms231810758","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:11:10Z","timestamp":1663279870000},"page":"10758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["In Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-9217","authenticated-orcid":false,"given":"Elodie","family":"Mareux","sequence":"first","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7033-831X","authenticated-orcid":false,"given":"Martine","family":"Lapalus","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Ben Saad","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Zelli","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, UMR CNRS 5063, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounia","family":"Lakli","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosra","family":"Riahi","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Almes","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Pediatric Hepatology & Pediatric Liver Transplant Department, Reference Center for Rare Pediatric Liver Diseases, FILFOIE, ERN Rare-Liver, Facult\u00e9 de M\u00e9decine Paris-Saclay, CHU Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Banet","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Mus\u00e9um National d\u2019Histoire Naturelle, UMR CNRS 7590, Institut de Min\u00e9ralogie, de Physique des Mat\u00e9riaux et de Cosmochimie (IMPMC), Sorbonne Universit\u00e9, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-1304","authenticated-orcid":false,"given":"Jean-Luc","family":"Decout","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, UMR CNRS 5063, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2867-0500","authenticated-orcid":false,"given":"Thomas","family":"Falgui\u00e8res","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jacquemin","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Pediatric Hepatology & Pediatric Liver Transplant Department, Reference Center for Rare Pediatric Liver Diseases, FILFOIE, ERN Rare-Liver, Facult\u00e9 de M\u00e9decine Paris-Saclay, CHU Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-3193","authenticated-orcid":false,"given":"Emmanuel","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 1193, Physiopathog\u00e9n\u00e8se et Traitement des Maladies du Foie, Universit\u00e9 Paris-Saclay, FHU Hepatinov, 91400 Orsay, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Pediatric Hepatology & Pediatric Liver Transplant Department, Reference Center for Rare Pediatric Liver Diseases, FILFOIE, ERN Rare-Liver, Facult\u00e9 de M\u00e9decine Paris-Saclay, CHU Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-4-1","article-title":"Progressive familial intrahepatic 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