Mmu-miR-92a-2-5p targets TLR2 to relieve Schistosoma japonicum-induced liver fibrosis.

According to conservative estimates, >230 million people are infected with schistosomiasis,which becomes one of the most common parasitic diseases. This study focuses on investigating in vivo and in vitro effects of mmu-miR-92a-2-5p in Schistosoma japonicum-induced liver fibrosis by targeting TLR2. Through bioinformatic analysis, the overexpression of TLR2 and the down-regulation of mmu-miR-92a-2-5p were revealed in the progression of S. japonicum-induced liver fibrosis. BALB/C mice were taken advantage to construct normal control and schistosomiasis liver fibrosis (SLF) model. The mice in model groups were transfected recombinant lentivirus (Lenti-mmu-miR-92a-2-5p or Lenti-NC) to alter the expression of mmu-miR-92a-2-5p in vivo. HE and Masson staining were employed to observe the pathological changes and collagenous fibrosis. QRT-PCR showed that mmu-miR-92a-2-5p was decreased while TLR2 was elevated in the infected groups. However, lenti-mmu-miR-92a-2-5p group could inhibit liver fibrosis. Then the effect of mmu-miR-92a-2-5p on S. japonicum-induced liver fibrosis including cell apoptosis rates, proliferation and proteins related to liver fibrosis was examined in NIH-3T3 mouse embryonic fibroblasts. Moreover, the association between mmu-miR-92a-2-5p and TLR2 was detected by dual-luciferase reporter gene assay and the expression of cytokines IL-4, IFN-γ and TNF-α in SLF model was detected by ELISA. Further, the knockout of TLR2 in C57BL/6J mice was used to confirm the association between mmu-miR-92a-2-5p and TLR2. Thus, these findings demonstrated that mmu-miR-92a-2-5p inhibited S. japonicum-induced liver fibrosis by targeting TLR2 in vitro and in vivo.