ZHOU Yi-long, YANG Shao-hua, ZHANG Chi, et al.LncRNA MALAT1 Modulates the Immunoreaction of Rats with Lipopolysaccharide-induced Sepsis by Targeting the miR-146a/NF-κB P65 Pathway.Journal of Sichuan University (Medical Science Edition),2018;49(6):865-870
LncRNA MALAT1 Modulates the Immunoreaction of Rats with Lipopolysaccharide-induced Sepsis by Targeting the miR-146a/NF-κB P65 Pathway
Objective To determine the regulatory and molecular mechanism of lncRNA MALAT1 in response to sepsis induced by lipopolysaccharide (LPS) in rats. Methods The expressions of lncRNA MALAT1 and miR-146a in U937 cells and peripheral blood samples of the rats with and without LPS-induced sepsis were detected using quantitative real-time reverse transcription PCR (qRT-PCR). The relationship between lncRNA MALAT1 and miR-146a was affirmed through luciferase assay. The expressions of p-P65, P65, TNF-α and iNOS were tested by Western blot. The expressions of TNF-α and iNOS in the lung tissues of the rats were measured by immunohistochemistry. Results The rats with LPS-induced sepsis had higher expressions of lncRNA MALAT1 in U937 cells than those without sepsis (P<0.001). In comparison with scramble, si-MALAT1 attenuated the expression of lncRNA MALAT1 and increased the expression of miR-146a (P<0.001). MiR-146a was the target of lncRNA MALAT1. si-MALAT1 decreased the p-P65/P65 ratio and and the expressions of TNF-α and iNOS in the rats with LPS-induced sepsis. In contrast, miR-146a inhibitor increased p-P65/P65 ratio and the expressions of TNF-α and iNOS in the rats with LPS-induced septis (P<0.001). Co-transfection with si-MALAT1 attenuated the elevated level of p-P65/P65 ratio and expressions of TNF-α and iNOS resulting from miR-146a inhibitor (P<0.001). LPS and scramble decreased the expression of miR-146a and increased the p-P65/P65 ratio compared with the healthy controls (P<0.01). Compared with scramble, si-MALAT1 increased the expression of miR-146a and attenuated the p-P65/P65 ratio (P<0.01). Higher numbers of TNF-α and iNOS positive cells were found in those with LPS-induced sepsis and those with scramble interventions (P<0.001). Compared with scramble, si-MALAT1 reduced the number of TNF-α and iNOS positive cells (P<0.01). Conclusion LncRNA MALAT1 modulates the immunoreaction of rats with LPS -induced sepsis by targeting miR-146a/NF-κB P65.
