{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:01:34Z","timestamp":1791874894320,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803606"],"award-info":[{"award-number":["81803606"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the role of zinc\u2010finger protein 281 (ZNF281), a novel molecule, in ethanol\u2010induced hepatocyte senescence and uncovered the potential mechanism. Real\u2010time PCR, Western blot, immunofluorescence staining, and enzyme\u2010linked immunosorbent assay were performed to explore the role of ZNF281 in hepatocyte senescence. ZNF281 expression was upregulated in both alcohol\u2010fed mice livers and ethanol\u2010treated hepatocytes. Silence of ZNF281 in hepatocytes using siRNA mitigated ethanol\u2010caused decrease in cell viability and increased release of aspartate aminotransferase, alanine transaminase, and lactate dehydrogenase. ZNF281 siRNA reduced senescence\u2010associated \u03b2\u2010galactosidase\u2010positive cells under ethanol exposure, abolished cell cycle arrest at G0\/G1 phase, and diminished senescence\u2010associated secretory phenotype and proinflammatory cytokines (IL\u20101\u03b2 and IL\u20106) release. At molecular level, ZNF281 deficiency altered the expression profile of senescence\u2010associated proteins including p53, p21, p16, high mobility group AT\u2010hook 1, and phospho\u2010histone H2A.X and telomerase\u2010associated regulatory factors including telomerase reverse transcriptase, telomeric repeat binding factor 1 (TRF1), and TRF2. ZNF281 knockdown promoted hepatocyte recovery from ethanol\u2010induced mitochondrial dysfunction and ROS production, which was correlated with rescuing HK2\u2010PINK1\/Parkin signalling\u2010mediated mitophagy. Mechanistically, ZNF281 directly bound to 5\u2032\u2010GGCGGCGGGCGG\u20103\u2032 motif within HK2 promoter region and transcriptionally repressed HK2 expression. Systematic ZNF281 knockdown by adeno\u2010associated virus encoding ZNF281 shRNA protected mice from alcohol feeding\u2010caused hepatocyte injury and senescence. This study provides a novel factor ZNF281 as a driver of hepatocyte senescence during alcoholic liver disease.<\/jats:p>","DOI":"10.1111\/cpr.13378","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T03:26:45Z","timestamp":1670988405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["<scp>ZNF281<\/scp>\n                    drives hepatocyte senescence in alcoholic liver disease by reducing\n                    <scp>HK2<\/scp>\n                    \u2010stabilized\u00a0\n                    <scp>PINK1<\/scp>\n                    \/Parkin\u2010mediated mitophagy"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3775-604X","authenticated-orcid":false,"given":"Chunfeng","family":"Lu","sequence":"first","affiliation":[{"name":"School of Pharmacy Nantong University  Nantong 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