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Previous studies have shown that runt\u2010related transcription factor 2 (Runx2) is associated with the development of non\u2010alcoholic fatty liver disease, while its specific role in HSC activation and hepatic fibrosis remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Approach and results<\/jats:title><jats:p>In this study, we found that Runx2 expression was significantly upregulated in human liver fibrosis with different aetiologies. Runx2 expression was also gradually elevated in mouse liver during fibrosis, and Runx2 was mainly expressed in the activated HSC. Knockdown of Runx2 in HSC markedly alleviated CCl<jats:sub>4<\/jats:sub>\u2010induced, 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine\u2010induced or methionine\u2010choline deficient (MCD)\u2010induced liver fibrosis, while hepatic overexpression of Runx2 via HBAAV\u2010Runx2 or VA\u2010Lip\u2010Runx2 injection exacerbated CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis. In vitro analysis demonstrated that Runx2 promoted HSC activation and proliferation, whereas Runx2 knockdown in HSC suppressed these effects. RNA\u2010seq and Runx2 ChIP\u2010seq analysis demonstrated that Runx2 could promote integrin alpha\u2010V (<jats:italic>Itgav<\/jats:italic>) expression by binding to its promoter. Blockade of <jats:italic>Itgav<\/jats:italic> attenuated Runx2\u2010induced HSC activation and liver fibrosis. Additionally, we found that cytokines (TGF\u2010\u03b21, PDGF, EGF) promote the expression and nuclear translocation of Runx2 through protein kinase A (PKA) in HSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Runx2 is critical for HSC activation via transcriptionally regulating <jats:italic>Itgav<\/jats:italic> expression during liver fibrosis, and may be a promising therapeutic target for liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1316","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T10:14:05Z","timestamp":1688552045000},"source":"Crossref","is-referenced-by-count":47,"title":["Runx2 activates hepatic stellate cells to promote liver fibrosis via transcriptionally regulating <i>Itgav<\/i> expression"],"prefix":"10.1002","volume":"13","author":[{"given":"Li","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Chongqing Medical 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