单位:[1]Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing 100050, China临床科室国家中心肝病分中心首都医科大学附属北京友谊医院[2]Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100050, China
Profibrogenesis cytokine, transforming growth factor- (TGF-) beta 1, induces hepatic progenitors experiencing epithelial to mesenchymal transition (EMT) to matrix synthesis cells, even tumor initiating cells. Our previous data found that epidermal growth factor (EGF) blocks and reverses TGF-beta 1-induced transition. The aim of this study is to determine the characteristic changes of hepatic progenitors after TGF-beta 1-induced transition and EGF-induced reversion. Hepatic oval cells, rat hepatic progenitors, were isolated from rats fed a choline-deficient diet supplemented with ethionine. TGF-beta 1-containing medium was used for inducing EMT, while EGF-containing medium was used for reversing EMT. During TGF-beta 1-induced transition and EGF-induced reversion, hepatic oval cells sustained their progenitor cell marker expression, including alpha-fetoprotein, albumin, and cytokeratin-19. The proliferation ability and differentiation potential of these cells were suppressed by TGF-beta 1, while EGF resumed these capacities to the level similar to the control cells. RNA microarray analysis showed that most of the genes with significant changes after TGF-beta 1 incubation were recovered by EGF. Signal pathway analysis revealed that TGF-beta 1 impaired the pathways of cell cycle and cytochrome P450 detoxification, and EGF reverted TGF-beta 1 effects through activating MAPK and PI3K-Akt pathway. EGF reverses the characteristics impaired by TGF-beta 1 in hepatic oval cells, serving as a protective cytokine to hepatic progenitors.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81100294, 81270519]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [Z111107054511064]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7132095]; Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges Under Beijing Municipality [IDHT20150502]
第一作者单位:[1]Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing 100050, China[2]Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100050, China
通讯作者:
通讯机构:[1]Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing 100050, China[2]Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100050, China
推荐引用方式(GB/T 7714):
Wang Ping,Cong Min,Liu Tianhui,et al.The Characteristics Variation of Hepatic Progenitors after TGF-beta 1-Induced Transition and EGF-Induced Reversion[J].STEM CELLS INTERNATIONAL.2016,2016:doi:10.1155/2016/6304385.
APA:
Wang, Ping,Cong, Min,Liu, Tianhui,Yang, Aiting,Sun, Guangyong...&You, Hong.(2016).The Characteristics Variation of Hepatic Progenitors after TGF-beta 1-Induced Transition and EGF-Induced Reversion.STEM CELLS INTERNATIONAL,2016,
MLA:
Wang, Ping,et al."The Characteristics Variation of Hepatic Progenitors after TGF-beta 1-Induced Transition and EGF-Induced Reversion".STEM CELLS INTERNATIONAL 2016.(2016)