Upregulation of KSRP by miR‐27b attenuates schistosomiasis‐induced hepatic fibrosis by targeting TGF‐β1

다국어 초록 (Multilingual Abstract)

Hepatic stellate cells (HSCs) are the main effectors for various types of hepatic fibrosis, including Schistosome‐induced hepatic fibrosis. Multiple inflammatory cytokines/chemokines, such as transforming growth factor‐β1 (TGF‐β1), activate HSCs, and contribute to the development of hepatic fibrosis. MicroRNAs regulate gene expression at the posttranscriptional level and are involved in regulation of inflammatory cytokine/chemokine synthesis. In this study, we showed that soluble egg antigen (SEA) stimulation and Schistosoma japonicum infection downregulate miR‐27b expression and increase KH‐type splicing regulatory protein (KSRP) mRNA and protein levels in vitro and in vivo. miR‐27b regulates the stabilization of TGF‐β1 mRNA through targeting KSRP by interacting with their AU‐rich elements in hepatocytes and non‐parenchymal cells, which has an effect on the activation of HSCs. Importantly, our results have shown that either knockdown miR‐27b or overexpression of KSRP attenuates S. japonicum‐induced hepatic fibrosis in vivo. Therefore, our study highlights the crucial role of miR‐27b and KSRP in the negative regulation of immune reactions in hepatocyte and non‐parenchymal cells in response to SEA stimulation and S. japonicum infection. It reveals that manipulation of miR‐27b or KSRP might be a useful strategy not only for treating Schistosome‐induced hepatic fibrosis but also for curing hepatic fibrosis in general.