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  • Title: Depleting microRNA-146a-3p attenuates lipopolysaccharide-induced acute lung injury via up-regulating SIRT1 and mediating NF-κB pathway.
    Author: Yang Y, Li L.
    Journal: J Drug Target; 2021 Apr; 29(4):420-429. PubMed ID: 33185125.
    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.
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