{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:21:42Z","timestamp":1768515702249,"version":"3.49.0"},"reference-count":30,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81670815"],"award-info":[{"award-number":["81670815"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2020A1515010124, 2021A1515010695"],"award-info":[{"award-number":["2020A1515010124, 2021A1515010695"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Innovation Strategy of Science and Technology Plan of Guangdong Province","award":["2019A030317011"],"award-info":[{"award-number":["2019A030317011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>The effects of hypoxia inducible factor-2\u03b1 (HIF-2\u03b1) deficiency on liver fibrosis have not been demonstrated in a fibrosis model induced by carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). We aimed to examine whether hepatocyte-specific HIF-2\u03b1 deletion could ameliorate CCl<jats:sub>4<\/jats:sub>-induced liver fibrosis in mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Hepatocyte-specific HIF-2\u03b1 knockout mice were created using an albumin promoter-driven Cre recombinase. HIF-2\u03b1 knockout (KO) mice and floxed control wild-type (WT) mice were fed a normal diet (ND) and received either twice weekly intraperitoneal injections of CCl<jats:sub>4<\/jats:sub> solution (CCl<jats:sub>4<\/jats:sub> dissolved in olive oil) or the corresponding amount of olive oil for 8 weeks. The indicators of liver function, glucose and lipid metabolism, and liver histology were compared among the different groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Hepatocyte-specific HIF-2\u03b1 knockout had no effect on the growth, liver function, glucose or lipid metabolism in mice. CCl<jats:sub>4<\/jats:sub>-treated KO and WT mice had a similar pattern of injury and inflammatory cell infiltration in the liver. Quantification of Masson staining, \u03b1-smooth muscle actin (\u03b1-SMA) immunohistochemistry, and the hydroxyproline (HYP) content revealed similar liver fibrosis levels between KO and WT mice injected intraperitoneally with CCl<jats:sub>4<\/jats:sub>. Immunohistochemistry analysis suggested that HIF-2\u03b1 was mainly expressed in the portal area and hepatic sinusoids but not in hepatocytes. Bioinformatics analyses further indicated that HIF-2\u03b1 expression was neither liver specific nor hepatocyte specific, and the effect of HIF-2\u03b1 in hepatocytes on liver fibrosis may not be as important as that in liver sinuses.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Hepatocyte HIF-2\u03b1 expression may not be a key factor in the initiation of liver fibrogenesis, and hepatocyte-specific deletion of HIF-2\u03b1 may not be the ideal therapeutic strategy for liver fibrosis.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.15191","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T09:08:52Z","timestamp":1680512932000},"page":"e15191","source":"Crossref","is-referenced-by-count":2,"title":["Hepatocyte-specific knockout of HIF-2\u03b1 cannot alleviate carbon tetrachloride-induced liver fibrosis in 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Gangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"issue":"2","key":"10.7717\/peerj.15191\/ref-1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nature 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