Premium
Antagonistic regulation of transmembrane 4 L6 family member 5 attenuates fibrotic phenotypes in CCl 4 ‐treated mice
Author(s) -
Kang Minkyung,
Jeong SooJin,
Park Sook Young,
Lee Hyo Jeong,
Kim Hyun Jeong,
Park Ki Hun,
Ye SangKyu,
Kim SungHoon,
Lee Jung Weon
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08452.x
Subject(s) - transforming growth factor , fibrosis , cirrhosis , biology , cancer research , hepatocellular carcinoma , epithelial–mesenchymal transition , epidermal growth factor , epidermal growth factor receptor , growth factor , in vivo , pathology , microbiology and biotechnology , downregulation and upregulation , receptor , medicine , biochemistry , gene
The development of liver fibrosis from chronic inflammation can involve epithelial–mesenchymal transition (EMT). Severe liver fibrosis can progress to cirrhosis, and further to hepatocellular carcinoma. Because the tetraspanin transmembrane 4 L6 family member 5 (TM4SF5) induces EMT and is highly expressed in hepatocellular carcinoma, it is of interest to investigate whether TM4SF5 expression is correlated with EMT processes during the development of fibrotic liver features. Using hepatic cells in vitro and a CCl 4 ‐mediated mouse liver in vivo model, we examined whether TM4SF5 is expressed during liver fibrosis mediated by CCl 4 administration and whether treatment with anti‐TM4SF5 reagent blocks the fibrotic liver features. Here, we found that TM4SF5 expression was induced by the transforming growth factor (TGF)β1 and epidermal growth factor signaling pathways in hepatocytes in vitro . In the CCl 4 ‐mediated mouse liver model, TM4SF5 was expressed during the liver fibrosis mediated by CCl 4 administration and correlated with α‐smooth muscle actin expression, collagen I deposition, and TGFβ1 and epidermal growth factor receptor signaling activation in fibrotic septa regions. Interestingly, treatment with anti‐TM4SF5 reagent blocked the TM4SF5‐mediated liver fibrotic features: the formation of fibrotic septa with α‐smooth muscle actin expression and collagen I deposition was attenuated by treatment with anti‐TM4SF5 reagent. These results suggest that TM4SF5 expression mediated by TGFβ1 and growth factor can facilitate fibrotic processes during chronic liver injuries. TM4SF5 is thus a candidate target for prevention of liver fibrosis following chronic liver injury.