Antagonistic regulation of transmembrane 4 L6 family member5 attenuates fibrotic phenotypes in CCl(4) -treated mice.
- Kang, Minkyung; Jeong, Soo-Jin; Park, Sook Young; Lee, Hyo Jeong; Kim, Hyun Jeong; Park, Ki Hun; Ye, Sang-Kyu; Kim, Sung-Hoon; Lee, Jung Weon
- Issue Date
- FEBS JOURNAL Vol.279 No.4, pp. 625-635
- 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
CCl4-mediated mouse liver in vivo model, we examined whether TM4SF5 is
expressed during liver fibrosis mediated by CCl4 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)b1 and epidermal growth factor signaling
pathways in hepatocytes in vitro. In the CCl4-mediated mouse liver model,
TM4SF5 was expressed during the liver fibrosis mediated by CCl4 administration
and correlated with a-smooth muscle actin expression, collagen I
deposition, and TGFb1 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 a-smooth muscle actin expression and collagen
I deposition was attenuated by treatment with anti-TM4SF5 reagent.
These results suggest that TM4SF5 expression mediated by TGFb1 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.
- Files in This Item: There are no files associated with this item.