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Hepatic inflammation and fibrosis induced by feeding with a diet deficient in methionine and choline (<jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content> diet) were markedly attenuated in <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> knockout mice when compared with wild\u2010type mice in the model of non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>). Hepatic cholangiocytes, myofibroblastic stellate cells and natural killer T cells were suggested to secret <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> in mice fed an <jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content> diet. Plasma and hepatic <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> levels were significantly higher in patients with <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> with advanced fibrosis than in those with early fibrosis. Hepatic <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> level was correlated with hepatic neutrophil infiltration and fibrosis in patients with alcoholic liver diseases. In those with hepatocellular carcinoma (<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> levels in plasma and <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> were prognostic factors after liver resection or transplantation. Downregulation of <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> inhibited tumor growth and lung metastasis in nude mice implanted with <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> cells. The single nucleotide polymorphism in the promoter region of the <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> gene was shown to be associated with activity of hepatitis in chronic hepatitis <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> patients, prognosis in patients with <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>, and growth and lung metastasis of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> xenografts in nude mice. <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> was reported to be a downstream effecter of <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>edgehog pathway, which modulates hepatic fibrosis and carcinogenesis. This review focuses on the roles of <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> in hepatic inflammation, fibrosis and cancer progression. Further elucidation of cellular interactions and molecular mechanisms associated with <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> actions may contribute to development of novel strategies for treatment of the liver diseases.<\/jats:p>","DOI":"10.1111\/hepr.12166","type":"journal-article","created":{"date-parts":[[2013,5,22]],"date-time":"2013-05-22T13:12:54Z","timestamp":1369228374000},"page":"22-30","source":"Crossref","is-referenced-by-count":83,"title":["Osteopontin: Versatile modulator of liver diseases"],"prefix":"10.1111","volume":"44","author":[{"given":"Sumiko","family":"Nagoshi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Saitama Medical Center Saitama Medical University  Saitama 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