{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:38:13Z","timestamp":1785407893990,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic hepatic diseases often involve fibrosis as a pivotal factor in their progression. This study investigates the regulatory mechanisms of Yin Yang 1 (YY1) in hepatic fibrosis. Our data reveal that YY1 binds to the prolyl hydroxylase domain 1 (<jats:italic>PHD1<\/jats:italic>) promoter. Rats treated with carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) display heightened fibrosis in liver tissues, accompanied by increased levels of YY1, PHD1, and the fibrosis marker alpha\u2010smooth muscle actin (\u03b1\u2010SMA). Elevated levels of YY1, PHD1, and \u03b1\u2010SMA are observed in the liver tissues of CCl<jats:sub>4<\/jats:sub>\u2010treated rats, primary hepatic stellate cells (HSCs) isolated from fibrotic liver tissues, and transforming growth factor beta\u20101 (TGF\u2010\u03b21)\u2010induced HSCs. The human HSC cell line LX\u20102, upon YY1 overexpression, exhibits enhanced TGF\u2010\u03b21\u2010induced activation, leading to increased expression of extracellular matrix (ECM)\u2010related proteins and inflammatory cytokines. YY1 silencing produces the opposite effect. YY1 exerts a positive regulatory effect on the activation of the phosphatidylinositol 3\u2010kinase (PI3K)\/protein kinase B (AKT) signaling pathway and PHD1 expression. PHD1 silencing rescues the promotion of YY1 in cell activation, ECM\u2010related protein expression, and inflammatory cytokine production in TGF\u2010\u03b21\u2010treated LX\u20102 cells. Overall, our findings propose a model wherein YY1 facilitates TGF\u2010\u03b21\u2010induced HSC activation, ECM\u2010related protein expression, and inflammatory cytokine production by promoting PHD1 expression and activating the PI3K\/AKT signaling pathway. This study positions YY1 as a promising therapeutic target for hepatic fibrosis.<\/jats:p>","DOI":"10.1111\/pin.13410","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T11:08:46Z","timestamp":1707908926000},"page":"197-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Yin Yang 1 facilitates the activation, inflammation, and extracellular matrix deposition of hepatic stellate cells in hepatic fibrosis"],"prefix":"10.1111","volume":"74","author":[{"given":"Xiao","family":"Fu","sequence":"first","affiliation":[{"name":"General Medicine Department The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Luo","sequence":"additional","affiliation":[{"name":"General Medicine Department The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 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