{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:11:02Z","timestamp":1790791862562,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:00:00Z","timestamp":1491350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170398"],"award-info":[{"award-number":["81170398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Placental growth factor (Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content>) is a member of the vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) family and is involved in pathological angiogenesis associated with chronic liver diseases. However, the precise mechanisms underlying Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> signalling contributing to liver fibrosis and angiogenesis remain largely unexplored. This study aimed to assess the effect of reducing Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> expression using small interfering <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms. Fibrosis was induced in mice by carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>) for 8 weeks, and mice were treated with Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> or non\u2010targeting control si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> starting two weeks after initiating <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> injections. The results showed that Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> was highly expressed in cirrhotic human and mice livers; which mainly distributed in activated hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s). Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> silencing robustly reduced liver inflammation, fibrosis, intrahepatic macrophage recruitment, and inhibited the activation of <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s <jats:italic>in vivo<\/jats:italic>. Moreover, Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010treated fibrotic mice showed diminished hepatic microvessel density and angiogenic factors, such as hypoxia\u2010inducible factor\u20101\u03b1 (<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1), <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> receptor\u20101. Moreover, down\u2010regulation of Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> with si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s inhibited the activation and proliferation of <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s. Mechanistically, overexpression of Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> in activated <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s was induced by hypoxia dependent on <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1, and Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> induces <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> activation and proliferation <jats:italic>via<\/jats:italic> activation the phosphatidylinositol 3\u2010kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K)\/Akt signalling pathways. These findings indicate that Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> plays an important role in liver fibrosis\u2010associated angiogenesis and that blockage of Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content> could be an effective strategy for chronic liver disease.<\/jats:p>","DOI":"10.1111\/jcmm.13158","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T18:01:16Z","timestamp":1491415276000},"page":"2370-2385","source":"Crossref","is-referenced-by-count":33,"title":["Placental growth factor silencing ameliorates liver fibrosis and angiogenesis and inhibits activation of hepatic stellate cells in a murine model of chronic liver disease"],"prefix":"10.1111","volume":"21","author":[{"given":"Xi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Geriatrics Zhongshan Hospital Fudan University Shanghai 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