EGF Suppresses the Initiation and Drives the Reversion of TGF-β1-induced Transition in Hepatic Oval Cells Showing the Plasticity of Progenitor Cells.
Transforming growth factor-β1 (TGF-β1) induces hepatic progenitors to tumor initiating cells through epithelial-mesenchymal transition (EMT), thus raising an important drawback for stem cell-based therapy. How to block and reverse TGF-β1-induced transition is crucial for progenitors' clinical application and carcinogenic prevention. Rat adult hepatic progenitors, hepatic oval cells, experienced E-cadherin to N-cadherin switch and changed to α-smooth muscle actin (α-SMA) positive cells after TGF-β1 incubation, indicating EMT. When TGF-β1 plus EGF were co-administrated to these cells, EGF dose-dependently suppressed the cadherin switch and α-SMA expression. Interestingly, if EGF was applied to TGF-β1-pretreated cells, the cells that have experienced EMT could return to their epithelial phenotype. Abruption of EGF receptor revealed that EGF exerted its blockage and reversal effects through phosphorylation of ERK1/2 and Akt. These findings suggest an important attribute of EGF on opposing and reversing TGF-β1 effects, indicating the plasticity of hepatic progenitors.
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.|Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China.
Ping
P
Wang
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Ai-Ting
AT
Yang
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Min
M
Cong
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Tian-Hui
TH
Liu
Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Dong
D
Zhang
Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Jian
J
Huang
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Xiao-Fei
XF
Tong
Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Sheng-Tao
ST
Zhu
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Yong
Y
Xu
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Shu-Zhen
SZ
Tang
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Bao-En
BE
Wang
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Hong
H
Ma
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Ji-Dong
JD
Jia
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.
Hong
H
You
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D015820:Cadherins; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor