Lentivirus-mediated over-expression of let-7b microRNA suppresses hepatic fibrosis in the mouse infected with Schistosoma japonicum

- Overexpression of let-7b in vivo relieves S. japonicum-induced liver pathological damage, inflammatory responses and liver fibrosis.
- Let-7b regulates the expression of TβRI in vivo and in vitro.

Transforming growth factor-β (TGF-β) signaling pathway is documented to participate in liver fibrosis via multifactorial mechanisms. microRNA Let-7b (Let-7b) has been proved to alleviate cell fibrosis through regulating TGF-β receptor I (TβRI), but whether it is involved in Schistosomiasis liver fibrosis (SLF) has not been determined. In the present, SLF mice model was used to investigate Let-7b's function and mechanism in SLF. We found that hepatic let-7b expression was continuously declined in SLF, accompanied by the induction of TGF-β pathway molecules (TGF-β1, TβRI), profibrogenic mediators (α-SMA, colla I), and Th1/Th2 cells response factors (IFN-γ, IL-4). When recombinant Lentivirus of let-7b (Lenti-let-7b) was transfected into S. japonicum-infected mice, the mice hepatic fibrosis was distinctly ameliorated, and TGF-β1, TβRI, α-SMA, and colla I expressions were remarkly decreased, mice serum IL-4 and IFN-γ levels were reduced. Similarly, over-expression of let-7b down-regulated the expression of TβRI in THP-1 cells transfected with let-7b mimics, while TβRI was up-regulated after treated with let-7b inhibitor. These findings suggested that let-7b is a negative regulator to SLF through downregulating TβRI, and inhibits Th1 and Th2 type cell immune response. This provides a novel potential therapeutic strategy for SFL prevention.

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