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However, its involvement in hepatic fibrosis remains unclear. In this study, we wanted to clarify, in vivo, the role of HBx protein in the development of liver fibrosis. Mice transgenic for the full-length HBx (FL-HBx) were used. To create liver fibrosis, FL-HBx transgenic and control mice were chronically exposed to carbon tetrachloride (CCl4). Modulation of the expression of proteins involved in matrix remodeling, hepatic metabolism and epithelial-mesenchymal transition (EMT) were investigated. In transgenic mice, FL-HBx expression potentiates CCl4-induced liver fibrosis with increased expression of proteins involved in matrix remodeling (Collagen1a, \u03b1-Sma, PdgfR-\u03b2, MMP-13). In FL-HBx transgenic mice, an increase in EMT was observed with a higher transcription of two inflammatory cytokines (TNF-\u03b1 and TGF-\u03b2) and a decrease of glutamine synthetase expression level. This was associated with a sustained cell cycle and hepatocyte polyploidy alteration consistent with p38 and ERK1\/2 overactivation, increase of PLK1 transcription, accumulation of SQSTM1\/p62 protein and increase expression of Beclin-1. This correlates with a higher expression of tumor progenitor cell markers (AFP, Ly6D and EpCam), indicating a higher risk of progression from fibrosis to hepatocellular carcinoma (HCC) in the presence of FL-HBx protein. In conclusion, our results show that FL-HBx protein enhances the development of liver fibrosis and contributes to the progression of liver disease from chronic hepatitis to HCC.<\/jats:p>","DOI":"10.1093\/carcin\/bgz109","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T19:13:44Z","timestamp":1559848424000},"page":"358-367","source":"Crossref","is-referenced-by-count":28,"title":["Hepatitis B virus X protein enhances the development of liver fibrosis and the expression of genes associated with epithelial-mesenchymal transitions and tumor progenitor cells"],"prefix":"10.1093","volume":"41","author":[{"given":"James","family":"Ahodantin","sequence":"first","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"},{"name":"Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"Lekbaby","sequence":"first","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"},{"name":"Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Bou Nader","sequence":"first","affiliation":[{"name":"Team Proliferation Stress and Liver Physiopathology, Genome and Cancer, Centre de Recherche des Cordeliers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm), Paris, France"},{"name":"Sorbonne Unversit\u00e9, USPC, Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Paris, France"},{"name":"Universit\u00e9 Paris Diderot, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Soussan","sequence":"first","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"},{"name":"Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Kremsdorf","sequence":"first","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"},{"name":"Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm, UMR1135), Sorbonne Universit\u00e9s, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"2020051404380314500_CIT0001","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1016\/j.jhep.2016.02.021","article-title":"Mechanisms of HBV-induced hepatocellular carcinoma","volume":"64","author":"Levrero","year":"2016","journal-title":"J. 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