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EGF Suppresses the Initiation and Drives the Reversion of TGF‐β1‐induced Transition in Hepatic Oval Cells Showing the Plasticity of Progenitor Cells
Author(s) -
Wang Ping,
Yang AITing,
Cong Min,
Liu TianHui,
Zhang Dong,
Huang Jian,
Tong XiaoFei,
Zhu ShengTao,
Xu Yong,
Tang ShuZhen,
Wang BaoEn,
Ma Hong,
Jia JiDong,
You Hong
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24962
Subject(s) - reversion , progenitor cell , microbiology and biotechnology , plasticity , progenitor , transforming growth factor , transition (genetics) , biology , chemistry , stem cell , biochemistry , phenotype , physics , gene , thermodynamics
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. J. Cell. Physiol. 230: 2362–2370, 2015. © 2015 Wiley Periodicals, Inc.