In vivo transfection of C/EBP‐α gene could ameliorate CCL₄‐induced hepatic fibrosis in mice

AIM: Hepatic stellate cells (HSCs) play a key role in liver fibrosis. CCAAT/enhancer-binding proteins-alpha (C/EBP-alpha) can inhibit HSCs activation in vitro, as described in our previous study. However, little is known about the in vivo effect of C/EBP-alpha gene in hepatic fibrosis. METHODS: Male BALB/c mice were injected by hydrodynamic protocol with pIRES2-EGFP-C/EBPalpha expression vector from the first to the fourth week (early intervention) or from the ninth to the 12th week (late intervention) after CCl(4) injection, respectively. Successful transfection of vector and the expression of C/EBP-alpha were confirmed with the appearance of green fluorescence in liver cells, immunohistochemical staining and the western blot. RESULTS: High expression of C/EBP-alpha gene in liver cells, especially in non-parenchymal cells, could reduce the content of collagens by 82.5% and 72.3% (Sirius red staining + image analysis) and the content of hydroxyproline by 56.3% and 51.6%, respectively, in the early and late intervention experiments. CONCLUSION: It is evident that exogenous C/EBP-alpha gene has an early and late intervention role in mice liver fibrosis.