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CCAAT\/enhancer binding protein \u03b1 (CEBPA), as a versatile ligand-independent transcriptional factor, has an important function in myeloid cells, and is under clinical evaluation for cancer therapy. CEBPA is also expressed in hepatocytes and regulates glucolipid homeostasis; however, the role of hepatocyte-specific CEBPA in modulating liver fibrosis progression is largely unknown. Here, hepatic CEBPA expression was found to be decreased during MASH progression both in humans and mice, and hepatic\n                    <jats:italic>CEBPA<\/jats:italic>\n                    mRNA was negatively correlated with MASH fibrosis in the human liver.\n                    <jats:italic>Cebpa<\/jats:italic>\n                    <jats:sup>\u0394Hep<\/jats:sup>\n                    mice had markedly enhanced liver fibrosis induced by a high-fat, high-cholesterol, high-fructose diet or carbon tetrachloride. Temporal and spatial hepatocyte-specific CEBPA loss at the progressive stage of MASH in\n                    <jats:italic>Cebpa<\/jats:italic>\n                    <jats:sup>\u0394Hep,ERT2<\/jats:sup>\n                    mice functionally promoted liver fibrosis. Mechanistically, hepatocyte CEBPA directly repressed\n                    <jats:italic>Spp1<\/jats:italic>\n                    transactivation to reduce the secretion of osteopontin, a fibrogenesis inducer of hepatic stellate cells. Forced hepatocyte-specific CEBPA expression reduced MASH-associated liver fibrosis. These results demonstrate an important role for hepatocyte-specific CEBPA in liver fibrosis progression, and may help guide the therapeutic discoveries targeting hepatocyte CEBPA for the treatment of liver fibrosis.\n                  <\/jats:p>","DOI":"10.1172\/jci166731","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T14:00:32Z","timestamp":1711893632000},"source":"Crossref","is-referenced-by-count":39,"title":["Hepatocyte-specific CCAAT\/enhancer binding protein \u03b1 restricts liver fibrosis progression"],"prefix":"10.1172","volume":"134","author":[{"given":"Tingting","family":"Yan","sequence":"first","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA."},{"name":"State Key Laboratory of Natural Medicines, Laboratory of Metabolic Regulation and Drug Target Discovery, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Yan","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA."},{"name":"State Key Laboratory of Natural Medicines, Laboratory of Metabolic Regulation and Drug Target Discovery, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangliu","family":"Xia","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vorthon","family":"Sawaswong","sequence":"additional","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 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