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In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka ( Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks\u2019 postexposure. Within 6 weeks, hepatic fibrosis\/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of transforming growth factor beta 1 ( tgfb1), tgfb receptor 2, mothers against decapentaplegic homolog 3 ( smad3a), smad3b, beta-catenin ( ctnnb1), myc, matrix metalloproteinase ( mmp2), mmp14a, mmp14b, tissue inhibitors of metalloproteinase ( timp) 2a, timp2b, timp3, collagen type I alpha 1a ( col1a1a), and col1a1b and a less pronounced increase in mmp13 and col4a1 expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-\u03b21. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis and demonstrated that the TGF-\u03b2 pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis.<\/jats:p>","DOI":"10.1177\/0192623312464308","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T20:56:19Z","timestamp":1354222579000},"page":"744-760","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Anchoring Hepatic Gene Expression with Development of Fibrosis and Neoplasia in a Toxicant-induced Fish Model of Liver Injury"],"prefix":"10.1177","volume":"41","author":[{"given":"Arnaud J.","family":"Van Wettere","sequence":"first","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA"},{"name":"Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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