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

microRNA-146a is involved in rSjP40-inhibited activation of LX-2 cells by targeting Smad4 expression
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microRNA-146a 通过靶向 Smad4 表达参与 rSjP40 抑制的 LX-2 细胞激活

DOI:
10.1002/jcb.27193
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发表时间:
2018-11-01
影响因子:
4
通讯作者:
Duan, Yinong
Duan, Yinong
中科院分区:
生物学2区
文献类型:
--
作者:
Zhu, Dandan;Hu, Bin;Duan, Yinong

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研究表明,重组日本血吸虫P40蛋白(rSjP 40)可通过TGF-1/Smads信号通路抑制肝星状细胞(HSC)的活化。由于多种microRNA通过靶向Smads在HSC活化和肝纤维化过程中发挥重要作用,我们试图寻找可能参与rSjP 40诱导的HSC活化抑制的潜在microRNA。利用实时荧光定量PCR方法,我们发现rSjP 40可以诱导LX-2细胞中miR-146 a的表达。miR-146 a抑制剂可部分恢复rSjP 40诱导的LX-2细胞中Smad 4和-SMA的下调表达水平。miR-146 a可通过靶向Smad 4参与rSjP 40诱导的HSC活化抑制。这些结果为探讨rSjP 40调控肝纤维化的可能机制提供了新的思路。
Previous studies have demonstrated that the recombinant Schistosoma japonicum protein P40 (rSjP40) could inhibit activation of hepatic stellate cells (HSCs)through the TGF-1/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 -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.