{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:15:39Z","timestamp":1790972139776,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1126,"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":[[2012,8]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Cl\u2212\/HCO<\/jats:bold>\n                      Symbol\n                      <jats:bold>anion exchanger 2 (AE2) participates in intracellular pH homeostasis and secretin-stimulated biliary bicarbonate secretion.<\/jats:bold>\n                      <jats:bold>AE2\/SLC4A2<\/jats:bold>\n                      <jats:bold>gene expression is reduced in liver and blood mononuclear cells from patients with primary biliary cirrhosis (PBC). Our previous findings of hepatic and immunological features mimicking PBC in<\/jats:bold>\n                      <jats:bold>Ae2<\/jats:bold>\n                      <jats:bold>-deficient mice strongly suggest that decreased AE2 expression might be involved in the pathogenesis of PBC. Here, we tested the potential role of microRNA 506 (miR-506) \u2014 predicted as candidate to target AE2 mRNA \u2014 for the decreased expression of AE2 in PBC. Real-time quantitative polymerase chain reaction showed that miR-506 expression is increased in PBC livers versus normal liver specimens.<\/jats:bold>\n                      <jats:bold>In situ<\/jats:bold>\n                      <jats:bold>hybridization in liver sections confirmed that miR-506 is up-regulated in the intrahepatic bile ducts of PBC livers, compared with normal and primary sclerosing cholangitis livers. Precursor-mediated overexpression of miR-506 in SV40-immortalized normal human cholangiocytes (H69 cells) led to decreased AE2 protein expression and activity, as indicated by immunoblotting and microfluorimetry, respectively. Moreover, miR-506 overexpression in three-dimensional (3D)-cultured H69 cholangiocytes blocked the secretin-stimulated expansion of cystic structures developed under the 3D conditions. Luciferase assays and site-directed mutagenesis demonstrated that miR-506 specifically may bind the 3\u2032untranslated region (3\u2032UTR) of AE2 messenger RNA (mRNA) and prevent protein translation. Finally, cultured PBC cholangiocytes showed decreased AE2 activity, together with miR-506 overexpression, compared to normal human cholangiocytes, and transfection of PBC cholangiocytes with anti-miR-506 was able to improve their AE2 activity.<\/jats:bold>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      <jats:bold>miR-506 is up-regulated in cholangiocytes from PBC patients, binds the 3\u2032UTR region of AE2 mRNA, and prevents protein translation, leading to diminished AE2 activity and impaired biliary secretory functions. In view of the putative pathogenic role of decreased AE2 in PBC, miR-506 may constitute a potential therapeutic target for this disease. (HEPATOLOGY 2012)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.25691","type":"journal-article","created":{"date-parts":[[2012,3,3]],"date-time":"2012-03-03T20:27:43Z","timestamp":1330806463000},"page":"687-697","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":214,"title":["Up-regulation of microRNA 506 leads to decreased Cl\u2212\/HCO3 \u2212 anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis"],"prefix":"10.1097","volume":"56","author":[{"given":"Jes\u00fas M.","family":"Banales","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"S\u00e1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"\u00dariz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarai","family":"Sarvide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aura D.","family":"Urribarri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Splinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Tietz Bogert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Bujanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Prieto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan F.","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas F.","family":"LaRusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-32-20241201","doi-asserted-by":"crossref","first-page":"745758","DOI":"10.1016\/j.jhep.2009.11.027","article-title":"Primary biliary cirrhosis: a 2010 update.","volume":"52","author":"Poupon","year":"2010","journal-title":"J Hepatol"},{"key":"R2-32-20241201","doi-asserted-by":"crossref","first-page":"283307","DOI":"10.1007\/s00281-009-0164-5","article-title":"Primary biliary cirrhosis.","volume":"31","author":"Hohenester","year":"2009","journal-title":"Semin Immunopathol"},{"key":"R3-32-20241201","doi-asserted-by":"crossref","first-page":"401408","DOI":"10.1016\/j.dld.2010.02.014","article-title":"Update on primary biliary cirrhosis.","volume":"42","author":"Invernizzi","year":"2010","journal-title":"Dig Liver Dis"},{"key":"R4-32-20241201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-3-1","article-title":"Primary biliary cirrhosis.","volume":"3","author":"Kumagi","year":"2008","journal-title":"Orphanet J Rare Dis"},{"key":"R5-32-20241201","doi-asserted-by":"crossref","first-page":"15481554","DOI":"10.1056\/NEJM199105303242204","article-title":"A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. 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