{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:48:49Z","timestamp":1789469329458,"version":"build-2803163510"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":32,"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":[[2015,10]]},"abstract":"<jats:p>Prohibitin\u20101 (PHB1) is an evolutionarily conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a diverse role for PHB1 in the pathogenesis of obesity, cancer, and inflammatory bowel disease, among others. Data presented here suggest that PHB1 is also linked to cholestatic liver disease. Expression of PHB1 is markedly reduced in patients with primary biliary cirrhosis and biliary atresia or with Alagille syndrome, two major pediatric cholestatic conditions. In the experimental model of bile duct ligation, silencing of PHB1 induced liver fibrosis, reduced animal survival, and induced bile duct proliferation. Importantly, the modulatory effect of PHB1 is not dependent on its known mitochondrial function. Also, PHB1 interacts with histone deacetylase 4 (HDAC4) in the presence of bile acids. Hence, PHB1 depletion leads to increased nuclear HDAC4 content and its associated epigenetic changes. Remarkably, HDAC4 silencing and the administration of the HDAC inhibitor parthenolide during obstructive cholestasis <jats:italic toggle=\"yes\">in vivo<\/jats:italic> promote genomic reprogramming, leading to regression of the fibrotic phenotype in liver\u2010specific <jats:italic toggle=\"yes\">Phb1<\/jats:italic> knockout mice. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: PHB1 is an important mediator of cholestatic liver injury that regulates the activity of HDAC4, which controls specific epigenetic markers; these results identify potential novel strategies to treat liver injury and fibrosis, particularly as a consequence of chronic cholestasis. (H<jats:sc>epatology<\/jats:sc> 2015;62:1237\u20101248)<\/jats:p>","DOI":"10.1002\/hep.27959","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T08:06:30Z","timestamp":1435219590000},"page":"1237-1248","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":33,"title":["Histone deacetylase 4 promotes cholestatic liver injury in the absence of prohibitin\u20101"],"prefix":"10.1097","volume":"62","author":[{"given":"Luc\u00eda","family":"Barbier\u2010Torres","sequence":"first","affiliation":[{"name":"CIC bioGUNE, Metabolomics Unit,Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd),Bizkaia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara","family":"Beraza","sequence":"additional","affiliation":[{"name":"CIC bioGUNE, Metabolomics Unit,Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y 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Donostia University Hospital (HUD), University of the Basque Country (UPV\/EHU), Ikerbasque, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd),San Sebastian,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Azienda Ospedaliero\u2010Universitaria and University of Modena and Reggio Emilia,Modena,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Caballer\u00eda","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Cl\u00ednic, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd),IDIBAPS,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Alvarez","sequence":"additional","affiliation":[{"name":"La Paz University Hospital Health Research 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