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SjP40 is a major egg antigen of Schistosoma japonicum. In the present study, the authors investigated the effect of SjP40 in vitro on transforming growth factor-β1 (TGF-β1)- stimulated hepatic stellate cells (HSCs). LX-2, an immortalized human HSC line, was treated with purified recombinant SjP40 (rSjP40) in the presence or absence of TGF-β1. Quantitative real-time polymerase chain reaction and western blot analysis were performed to determine messenger ribonucleic acid and protein of fibrogenic genes and TGF-β signaling pathway. The results showed that expression of fibrogenic genes was significantly reduced by rSjP40. Furthermore, rSjP40 also suppressed the TGF-β1-induced upregulation of Smads and ERK proteins. We also found that the effect of rSjP40 on HSCs was similar to SB431542, an inhibitor of type I TGF-β receptor. In conclusion, the data suggest that SjP40 attenuates HSC activation, which might be, at least in part, mediated by inhibiting the TGF-β and ERK signaling pathways.

BackgroundIn the process of hepatic fibrosis, hepatic stellate cells (HSCs) can be activated by many inflammatory cytokines. The transforming growth factor-β1 (TGF-β1) is one of the main profibrogenic mediators. Recently, some studies have also shown that microRNAs (miRNAs) play essential roles in the progress of liver fibrosis by being involved in the differentiation, fat metabolism and ECM production of HSCs.MethodsThe expression of miR-454 in LX-2 cells treated with TGF-β1 and in the fibrotic livers with Schistosoma japonicum infection was detected by qRT-PCR. The role of miR-454 on LX-2 cells was then analyzed by Western blot, flow cytometry and luciferase assay.ResultsThe results showed that the expression of miR-454 was down-regulated in the TGF-β1-treated LX-2 cells and miR-454 could inhibit the activation of HSCs by directly targeting Smad4. However, we found that miR-454 had no effect on cell cycle and cell proliferation in TGF-β1-treated LX-2. Besides these, miR-454 was found to be regulated in the process of Schistosoma japonicum infection.ConclusionsAll the results suggested that miR-454 could provide a novel therapeutic approach for treating liver fibrosis, especially the liver fibrosis induced by Schistosoma japonicum.

BackgroundThe induction of hepatic stellate cell (HSC) apoptosis has potential as a potent strategy to diminish the progression of liver fibrosis. Previous studies have demonstrated the ability of soluble egg antigens (SEA) from schistosomes to inhibit HSC activation and to induce apoptosis in vitro. In this study, we aimed to explore the mechanism of SEA-induced apoptosis in HSCs.Methodology/Principal FindingsIn this study, we found that SEA could upregulate p53 and DR5 and downregulate the p-Akt. The apoptosis of HSCs induced by SEA could be reduced in HSCs that were treated with p53-specific siRNA and in HSCs that were treated with DR5-specific shRNA. In addition, GW501516, which enhances the expression of Akt, could also decrease the SEA-induced HSC apoptosis. We also found that the increased expression of p53 and DR5 induced by SEA through Mdm2 were reduced by GW501516.Conclusions/SignificanceOur data suggest that SEA can induce HSC apoptosis by downregulating Akt expression and upregulating p53-dependent DR5 expression.