The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion

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 t...

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Main Authors: Ping Wang, Min Cong, Tianhui Liu, Aiting Yang, Guangyong Sun, Dong Zhang, Jian Huang, Shujie Sun, Jia Mao, Hong Ma, Jidong Jia, Hong You
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/6304385
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author Ping Wang
Min Cong
Tianhui Liu
Aiting Yang
Guangyong Sun
Dong Zhang
Jian Huang
Shujie Sun
Jia Mao
Hong Ma
Jidong Jia
Hong You
author_facet Ping Wang
Min Cong
Tianhui Liu
Aiting Yang
Guangyong Sun
Dong Zhang
Jian Huang
Shujie Sun
Jia Mao
Hong Ma
Jidong Jia
Hong You
author_sort Ping Wang
collection DOAJ
description 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.
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spelling doaj-art-e3df4206ecf2454d8614c2d6fb9319c62025-02-03T00:59:44ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/63043856304385The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced ReversionPing Wang0Min Cong1Tianhui Liu2Aiting Yang3Guangyong Sun4Dong Zhang5Jian Huang6Shujie Sun7Jia Mao8Hong Ma9Jidong Jia10Hong You11Liver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaLiver 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, ChinaProfibrogenesis 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.http://dx.doi.org/10.1155/2016/6304385
spellingShingle Ping Wang
Min Cong
Tianhui Liu
Aiting Yang
Guangyong Sun
Dong Zhang
Jian Huang
Shujie Sun
Jia Mao
Hong Ma
Jidong Jia
Hong You
The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion
Stem Cells International
title The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion
title_full The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion
title_fullStr The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion
title_full_unstemmed The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion
title_short The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion
title_sort characteristics variation of hepatic progenitors after tgf β1 induced transition and egf induced reversion
url http://dx.doi.org/10.1155/2016/6304385
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