{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:53:33Z","timestamp":1784303613341,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82425058"],"award-info":[{"award-number":["82425058"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0523100"],"award-info":[{"award-number":["2024ZD0523100"]}]},{"name":"Shanghai Municipal Science and Technology committee of Shanghai outstanding academic leaders plan","award":["22Xd1400600"],"award-info":[{"award-number":["22Xd1400600"]}]},{"name":"the Shanghai \u201cScience and Technology Innovation Action Plan\u201d Biomedical Science and Technology Support Special Project","award":["23S11900800"],"award-info":[{"award-number":["23S11900800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Acute liver injury (ALI) is a potentially life-threatening condition lacking effective clinical drugs. Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) is a key regulator of both inflammation and metabolism. In ALI, HIF-1\u03b1 expressions are upregulated, but the role of HIF-1\u03b1 in hepatocytes and whether it can be targeted remain unclear. Herein, clinical samples and ALI murine models including lipopolysaccharide\/D-galactosamine (LPS\/D-GalN), acetaminophen (APAP), and thioacetamide (TAA) revealed an increase in HIF-1\u03b1 expression and ferroptosis. Using HIF-1\u03b1 gain and loss of function mouse and hepatocyte culture models, we demonstrated that HIF-1\u03b1 upregulation exacerbated liver ferroptosis and injury. Mechanistically, HIF-1\u03b1\/transferrin receptor protein 1 (TFR1) axis drives hepatic iron overload, promoting ferroptotic cell death and liver injury. In addition, TFR1 inhibition reversed HIF-1\u03b1-induced ALI. Importantly, pharmacological inhibition of HIF-1\u03b1 and TFR1 significantly reduced ferroptosis and mitigated liver injury both in vivo and in vitro. Together, our findings demonstrate the pathological role of hepatic HIF-1\u03b1, which may serve as a promising target of therapeutic intervention.<\/jats:p>","DOI":"10.3390\/antiox15010081","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:01:29Z","timestamp":1767862889000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatic Hypoxia-Inducible Factor 1\u03b1 Mediates Ferroptosis via Transferrin Receptor 1 in Acute Liver Injury"],"prefix":"10.3390","volume":"15","author":[{"given":"Jiayu","family":"Yang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-1270","authenticated-orcid":false,"given":"Shichao","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Xia","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfang","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Ethnomedicine and Biofunctional Molecule Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linshi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.jhep.2018.01.008","article-title":"Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1 driven autoinflammation","volume":"68","author":"Gehrke","year":"2018","journal-title":"J. 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