National Taiwan Ocean University Institutional Repository:Item 987654321/34129
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题名: A zebrafish model of intrahepatic cholangiocarcinoma by dual expression of hepatitis B virus X and hepatitis C virus core protein in liver
作者: Wangta Liu;Jim-Ray Chen;Chih-Hao Hsu;Yen-Hsing Li;Yi-Meng Chen;Chien-Yuan Lin;Shin-Jie Huang;Zen-Kuei Chang;Yen-Chun Chen;Chi-Hsueh Lin;Hong-Yi Gong;Ching-Chun Lin;Koichi Kawakami;Jen-Leih Wu
贡献者: NTOU:Department of Aquaculture
國立臺灣海洋大學:水產養殖學系
日期: 2012-12
上传时间: 2013-10-03T03:24:48Z
出版者: Hepatology
摘要: Abstract:The mechanisms that mediate the initiation and development of intrahepatic cholangiocarcinoma (ICC) associated with hepatitis B and C virus (HBV and HCV, respectively) infection remain largely unclear. In this study we conditionally coexpressed hepatitis B virus X (HBx) and hepatitis C virus core (HCP) proteins in zebrafish livers, which caused fibrosis and consequently contributed to ICC formation at the age of 3 months. Suppressing the transgene expression by doxycycline (Dox) treatment resulted in the loss of ICC formation. The biomarker networks of zebrafish ICC identified by transcriptome sequencing and analysis were also frequently involved in the development of human neoplasms. The profiles of potential biomarker genes of zebrafish ICC were similar to those of human cholangiocarcinoma. Our data also showed that the pSmad3L oncogenic pathway was activated in HBx and HCP-induced ICC and included phosphorylation of p38 mitogen-activated proteinbase (MAPK) and p44/42 mitogen-activated protein kinase (ERK1/2), indicating the association with transforming growth factor beta 1 (TGF-β1) signaling pathway in ICC. Bile duct proliferation, fibrosis, and ICC were markedly reduced by knockdown of TGF-β1 by in vivo morpholinos injections. Conclusion: These results reveal that TGF-β1 plays an important role in HBx- and HCP-induced ICC development. This in vivo model is a potential approach to study the molecular events of fibrosis and ICC occurring in HBV and HCV infection. (Hepatology 2012;56:2268–2276)
關聯: 56(6), pp.2268-2276
URI: http://ntour.ntou.edu.tw/handle/987654321/34129
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