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微小 RNA-146a 通过靶向 Smad4 表达参与 rSjP40 抑制 LX-2 细胞的激活。

microRNA-146a is involved in rSjP40-inhibited activation of LX-2 cells by targeting Smad4 expression.

机构信息

Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.

Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, China.

出版信息

J Cell Biochem. 2018 Nov;119(11):9249-9253. doi: 10.1002/jcb.27193. Epub 2018 Jun 28.

Abstract

Previous studies have demonstrated that the recombinant Schistosoma japonicum protein P40 (rSjP40) could inhibit activation of hepatic stellate cells (HSCs) through the TGF-β1/Smads signaling pathway. Since multiple microRNAs could play essential roles in HSC activation and in the process of hepatic fibrosis through targeting Smads, we attempted to seek the potential microRNAs that could be involved in rSjP40-induced inhibition of HSC activation. Using the method of quantitative real-time PCR, we found that rSjP40 could induce miR-146a expression in LX-2 cells. The down-regulated expression levels of Smad4 and α-SMA in LX-2 cells induced by rSjP40 were partially restored by an miR-146a inhibitor. miR-146a can be involved in rSjP40-induced inhibition of HSC activation through targeting Smad4. These findings provide us a new idea to explore the potential mechanisms by which rSjP40 could regulate the process of hepatic fibrosis.

摘要

先前的研究已经证明,重组日本血吸虫蛋白 P40(rSjP40)可以通过 TGF-β1/Smads 信号通路抑制肝星状细胞(HSCs)的激活。由于多种 microRNAs 可以通过靶向 Smads 在 HSC 激活和肝纤维化过程中发挥重要作用,我们试图寻找可能参与 rSjP40 诱导的 HSC 激活抑制的潜在 microRNAs。通过实时定量 PCR 方法,我们发现 rSjP40 可以诱导 LX-2 细胞中 miR-146a 的表达。rSjP40 诱导的 LX-2 细胞中 Smad4 和 α-SMA 的下调表达水平部分被 miR-146a 抑制剂恢复。miR-146a 可以通过靶向 Smad4 参与 rSjP40 诱导的 HSC 激活抑制。这些发现为我们提供了一个新的思路来探索 rSjP40 调节肝纤维化过程的潜在机制。

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