title: The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion.
abstract: Profibrogenesis cytokine, transforming growth factor- (TGF-) β1, 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-β1-induced transition. The aim of this study is to determine the characteristic changes of hepatic progenitors after TGF-β1-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-β1-containing medium was used for inducing EMT, while EGF-containing medium was used for reversing EMT. During TGF-β1-induced transition and EGF-induced reversion, hepatic oval cells sustained their progenitor cell marker expression, including α-fetoprotein, albumin, and cytokeratin-19. The proliferation ability and differentiation potential of these cells were suppressed by TGF-β1, 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-β1 incubation were recovered by EGF. Signal pathway analysis revealed that TGF-β1 impaired the pathways of cell cycle and cytochrome P450 detoxification, and EGF reverted TGF-β1 effects through activating MAPK and PI3K-Akt pathway. EGF reverses the characteristics impaired by TGF-β1 in hepatic oval cells, serving as a protective cytokine to hepatic progenitors.
authors.affiliation: 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; Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100050, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Cong
authors.affiliation: 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.
authors.forename: Tianhui
authors.initials: T
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Aiting
authors.initials: A
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Guangyong
authors.initials: G
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Shujie
authors.initials: S
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: 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; Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100050, China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.affiliation: 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; Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100050, China.
authors.forename: Hong
authors.initials: H
authors.lastname: You