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Long Non-Coding RNA MEG3/microRNA-7b/NLR Pyrin Domain Containing 3 Axis Modulates Lipopolysaccharide-Induced Acute Lung Injury in a Mouse Model
29 Pages Posted: 20 Jun 2019
More...Abstract
Background: Acute lung injury (ALI) is still a serious health problem due to the limited current understanding of pathophysiology and treatment methods. This study investigated the roles of maternally expressed gene 3 (MEG3)/microRNA-7b (miR-7b)/NLR pyrin domain containing 3 (NLRP3) axis in lipopolysaccharide (LPS)-induced ALI.
Methods: Mouse alveolar macrophage NR8383 and mice were subjected to LPS treatment to establish ALI models in vitro and in vivo. Next, NLPR3 was silenced and miR-7b was overexpressed in LPS-induced R8383 cell model of ALI. The IL-18 and IL-1β levels, as well as Caspase-1, TNF-α and IL-6 protein levels were assayed. To further investigate the underlying mechanisms of NLPR3 in ALI, MEG3 was silenced and miR-7b was overexpressed in LPS-induced R8383 cell model of ALI, followed by in vivo experiments for further verification.
Results: NLRP3 was highly expressed in LPS-induced R8383 cell model of ALI. Silencing NLRP3 or overexpressing miR-7b inhibited IL-18 and IL-1β levels, as well as Caspase-1, TNF-α and IL-6 protein levels. MEG3 could sponge miR-7b, and silence of MEG3 or overexpression of miR-7b may downregulates the NLPR3 expression, thus reducing IL-18 and IL-1β, as well as Caspase-1, TNF-α and IL-6 levels. The in vivo experiments further confirmed the above findings.
Conclusion: After silencing MEG3, miR-7b binds more NLRP3 expression, thereby improving LPS-induced ALI.
Funding Statement: The authors state: "None."
Declaration of Interests: The authors declare that they have no conflicts of interest.
Ethics Approval Statement: The study protocols were approved by the Experimental Animal Ethics Committee of Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine.
Suggested Citation: Suggested Citation