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Published on: August 23, 2019
microRNA-146a is involved in rSjP40-inhibited activation of LX-2 cells by targeting Smad4 expression
Dandan Zhu1, Bin Hu1, Yonghua Zhou2
1Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
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.
Insights
Recombinant Schistosoma japonicum protein P40 (rSjP40) activates miR-146a, inhibiting hepatic stellate cell (HSC) activation. This suggests a new mechanism for rSjP40 in regulating hepatic fibrosis.
Area of Science:
- * Molecular biology
- * Cellular biology
- * Immunology
Background:
- * Hepatic stellate cell (HSC) activation drives hepatic fibrosis.
- * The recombinant Schistosoma japonicum protein P40 (rSjP40) inhibits HSC activation via the TGF-β1/Smads pathway.
- * MicroRNAs (miRNAs) are implicated in HSC activation and fibrosis by targeting Smads.
Purpose of the Study:
- * To identify potential microRNAs involved in rSjP40-mediated inhibition of HSC activation.
- * To elucidate the role of miR-146a in the rSjP40 signaling pathway.
- * To investigate the mechanism of rSjP40 in regulating hepatic fibrosis.
Main Methods:
- * Quantitative real-time PCR (qRT-PCR) to measure gene expression.
- * Treatment of LX-2 cells (a human HSC cell line) with rSjP40.
- * Use of an miR-146a inhibitor to assess its functional role.
Main Results:
- * rSjP40 significantly induced miR-146a expression in LX-2 cells.
- * Down-regulation of Smad4 and α-SMA induced by rSjP40 was partially reversed by an miR-146a inhibitor.
- * miR-146a targets Smad4, mediating rSjP40's inhibitory effect on HSC activation.
Conclusions:
- * miR-146a plays a crucial role in rSjP40-induced inhibition of HSC activation.
- * The mechanism involves miR-146a targeting Smad4.
- * Findings offer novel insights into rSjP40's antifibrotic potential and its regulatory pathways.
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