{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:41:22Z","timestamp":1771533682102,"version":"3.50.1"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5936,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale"},{"name":"Association Fran\u00e7aise pour la lutte contre la Mucoviscidose, Association de Lutte contre les Myopathies"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis (CF) gene product, functions as an adenosine 3\u2032,5\u2032\u2013cyclic monophosphate (cAMP)\u2013regulated chloride channel in the apical membrane of biliary epithelial cells, including gallbladder epithelial cells. It has been shown that \u25b3F508, the most common CF mutation, impedes CFTR trafficking to the apical surface of epithelial cells. To elucidate the mechanisms of CF biliary disease, we examined structural features, CFTR expression, and chloride transport properties in gallbladder epithelial cells from nine \u25b3F508 homozygous liver transplant recipients. Three CF patients had microgallbladders, characterized by severe histological abnormalities. Microgallbladder epithelial cells displayed aberrant immunolocalization of CFTR and of other normally apical proteins in the lateral domain of their plasma membrane and in their cytoplasm. This pattern was mimicked by chronic cholecystitis in non\u2013CF patients. In the 6 remaining CF patients, CFTR was predominantly apical in the gallbladder epithelium, consistent with the detection of a fully glycosylated form by Western blot. In CF as compared with non\u2013CF gallbladder epithelial cells in primary culture, chloride efflux was lower in response to cAMP and tended to be higher in response to exogenous adenosine 5\u2032\u2013triphosphate (ATP). The CF cells exhibited a residual cAMP\u2013dependent chloride secretion that was inversely correlated with ATP\u2013induced chloride secretion, and almost completely blunted in the cells derived from microgallbladders. Our results suggest that epithelial structural alterations aggravate \u25b3F508 CFTR mislocalization in the gallbladder epithelium. The associated decrease in residual cAMP\u2013dependent chloride secretion may contribute to biliary damage despite the up\u2013regulation of alternative chloride transport pathways.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510290634","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:25:40Z","timestamp":1090999540000},"page":"1624-1634","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Expression of Delta F508 Cystic Fibrosis Transmembrane Conductance Regulator Protein and Related Chloride Transport Properties in the Gallbladder Epithelium From Cystic Fibrosis Patients"],"prefix":"10.1097","volume":"29","author":[{"given":"Nathalie","family":"Dray-Charier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Yves","family":"Scoazec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Veissi\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Mergey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Capeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Soubrane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Housset","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.510290634-BIB1|cit1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"10.1002\/hep.510290634-BIB2|cit2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0022-3476(95)70022-6","article-title":"Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis","volume":"127","author":"Mack","year":"1995","journal-title":"J Pediatr"},{"key":"10.1002\/hep.510290634-BIB3|cit3","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/hep.1840060513","article-title":"Morphological findings in the liver of children with cystic fibrosis. 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