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rSjP40 suppresses hepatic stellate cell activation by promoting microRNA‐155 expression and inhibiting STAT5 and FOXO3a expression

机译:rSjP40通过促进microRNA‐155表达并抑制STAT5和FOXO3a表达来抑制肝星状细胞的活化

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摘要

Activation of hepatic stellate cells (HSCs) is the central event of the evolution of hepatic fibrosis. Schistosomiasis is one of the pathogenic factors which could induce hepatic fibrosis. Previous studies have shown that recombinant Schistosoma japonicum egg antigen P40 (rSjP40) can inhibit the activation and proliferation of HSCs. MicroRNA‐155 is one of the multifunctional noncoding RNA, which is involved in a series of important biological processes including cell development, proliferation, differentiation and apoptosis. Here, we try to observe the role of microRNA‐155 in rSjP40‐inhibited HSC activation and explore its potential mechanisms. We found that microRNA‐155 was raised in rSjP40‐treated HSCs, and further studies have shown that rSjP40 enhanced microRNA‐155 expression by inhibiting STAT5 transcription. Up‐regulated microRNA‐155 can down‐regulate the expression of FOXO3a and then participate in style="fixed-case">rSjP40‐inhibited expression of α‐smooth muscle actin (α‐ style="fixed-case">SMA) and collagen I. Furthermore, we observed micro style="fixed-case">RNA‐155 inhibitor could partially restore the down‐regulation of style="fixed-case">FOXO3a, α‐ style="fixed-case">SMA and collagen I expression in style="fixed-case">LX‐2 cells induced by style="fixed-case">rSjP40. Therefore, our research provides further insight into the mechanism by which style="fixed-case">rSjP40 could inhibit HSC activation via miR‐155.
机译:肝星状细胞(HSC)的激活是肝纤维化演变的中心事件。血吸虫病是可引起肝纤维化的致病因素之一。先前的研究表明,重组日本血吸虫卵抗原P40(rSjP40)可以抑制HSC的激活和增殖。 MicroRNA-155是一种多功能非编码RNA,它参与一系列重要的生物学过程,包括细胞发育,增殖,分化和凋亡。在这里,我们尝试观察microRNA-155在rSjP40抑制的HSC激活中的作用,并探讨其潜在机制。我们发现在经rSjP40处理的HSC中可产生microRNA-155,进一步的研究表明,rSjP40通过抑制STAT5转录增强了microRNA-155的表达。上调的microRNA‐155可以下调FOXO3a的表达,然后参与 style =“ fixed-case”> rSjP 40抑制的α-平滑肌肌动蛋白的表达(α- style = “ fixed-case”> SMA )和胶原蛋白I。此外,我们观察到micro style =“ fixed-case”> RNA ‐155抑制剂可以部分恢复 style =“ fixed-case”> FOXO 3a,α- style =“ fixed-case”> SMA 和 style =“ fixed-case”> LX rSjP 40诱导的> ‐2细胞。因此,我们的研究为 style =“ fixed-case”> rSjP 40通过miR-155抑制HSC激活的机制提供了进一步的认识。

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