[LncRNA MALAT1 Modulates the Immunoreaction of Rats with Lipopolysaccharide-induced Sepsis by Targeting the miR-146a/NF-κB P65 Pathway]

Yi-Long Zhou; Shao-Hua Yang; Chi Zhang; Bin Zhang; Xin-Juan Yang

[LncRNA MALAT1 Modulates the Immunoreaction of Rats with Lipopolysaccharide-induced Sepsis by Targeting the miR-146a/NF-κB P65 Pathway]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2018 Nov;49(6):865-870.

[Article in Chinese]

Authors

Yi-Long Zhou¹, Shao-Hua Yang², Chi Zhang¹, Bin Zhang², Xin-Juan Yang²

Affiliations

¹ Department of Emergency of Sanmenxia Central Hospital of Henan Province, Sanmenxia 472000, China.
² ICU of Sanmenxia Central Hospital of Henan Province, Sanmenxia 472000, China.

PMID: 32677394

Abstract

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).

Conclusions: LncRNA MALAT1 modulates the immunoreaction of rats with LPS -induced sepsis by targeting miR-146a/NF-κB P65.

Keywords: Immunoreaction; LncRNA MALAT1; NF-κB P65; Sepsis; miR-146a.

Publication types

English Abstract