Application of TGF-β1, TIMP-1 and TIMP-2 small interfering RNAs can alleviate CCl4-induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines.

The present study aimed to investigate the effects of TGF-β1, tissue inhibitor of metalloproteinase (TIMP)-1 small interfering (si)RNA and TIMP-2 siRNA on hepatic fibrosis in rats and explore the T helper (Th)1/Th2 balance. Moreover, IFN-γ, IL-4 and IL-13 are the main cytokines associated with Th1/Th2 responses and have significant influence on the progression of hepatic fibrosis. The expression levels of IFN-γ, IL-4 and IL-13 in rats with hepatic fibrosis that were treated with siRNAs against the aforementioned molecules were measured using various techniques including immunohistochemical staining, western blotting and reverse transcription-quantitative PCR. The principal outcomes revealed the downregulation of IFN-γ and the upregulation of IL-4 and IL-13 in the model group compared with the normal group. Moreover, the expression of IFN-γ was significantly increased, while IL-4 and IL-13 demonstrated no significant difference in the TGF-β1 siRNA treatment group compared with the model group. The TIMP-1 and TIMP-2 siRNA treatment groups exhibited significantly increased expression levels of IFN-γ, but lower expression levels of IL-4 and IL-13 compared with the model group. These results indicated that TIMP-1 and TIMP-2 were improved antifibrotic targets compared with TGF-β1.