Depleting microRNA-146a-3p attenuates lipopolysaccharide-induced acute lung injury via up-regulating SIRT1 and mediating NF-κB pathway. (21st April 2021)

• Record Type: Journal Article
• Authors: Yang, Yuxia; Li, Li
• Is Part Of: Journal of drug targeting. Volume 29:Number 4(2021)
• Page Start: 420
• Page End: 429
• Publication Date: 2021-04-21
• Subjects: Acute lung injury -- microRNA-146a-3p -- sirtuin-1 -- nuclear factor-kappa B pathway -- inflammation; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2020.1850738
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: Objective: The role of microRNAs (miRs) in acute lung injury (ALI) has been discussed. This study is to uncover the effects of miR-146a-3p/Sirtuin-1 (SIRT1)/Nuclear factor-kappa B (NF-κB) axis on ALI. Methods: Human normal lung epithelial cell line BEAS-2B was exposed to lipopolysaccharide (LPS) to establish an in vitro model of ALI. NF-κB expression, cell activity, apoptosis, inflammatory factors, oxidative stress indices were detected in LPS-induced BEAS-2B cells after miR-146a-3p was down-regulated or SIRT1 was up-regulated. ALI rat model was established and the NF-κB expression, wet/dry weight (W/D) ratio, pathological changes, pneumonocyte apoptosis, inflammatory factors, oxidative stress indices were detected in ALI rats after miR-146a-3p was down-regulated or SIRT1 was up-regulated. The target relationship between miR-146a-3p and SIRT1 was confirmed. Results: Reduced SIRT1 and raised miR-146a-3p were found in LPS-induced BEAS-2B cells and ALI rats. SIRT1-overexpressing or miR-146a-3p-underexpressing up-regulated NF-κB expression, promoted viability and inhibited apoptosis of LPS-induced BEAS-2B cells in vitro, and increased NF-κB expression, down-regulated the W/D ratio, attenuated pathological changes, suppressed apoptosis, and alleviated inflammatory response and oxidative stress in the lung of ALI rats. MiR-146a-3p directly binds to the 3′UTR of SIRT1 mRNA. Conclusion: Depleting miR-146a-3p improves ALI through up-regulating SIRT1 and mediating NF-κB pathway.