miR-135a-5p Suppresses TBK1 and Activates NRF2/TXNIP Antioxidant Pathway in LPS-Driven ALI in Mice

Comput Math Methods Med. 2022 Jul 20:2022:9088727. doi: 10.1155/2022/9088727. eCollection 2022.

Abstract

Objective: Acute inflammation and oxidative stress are present in large numbers in patients with acute lung injury (ALI). This investigation probed miR-135a-5p/TBK1 axis within ALI together with its new therapeutic target.

Methods: MLE-12 cultures were treated with lipopolysaccharide (LPS) and transfected with miR-135a-5p mimics or TBK1 vector. An ALI mouse model was also established. Analysis was done on the relationships between TBK1 and miR-135a-5p. Inflammatory components, SOD, MDA, and ROS content were all assessed.

Results: Obvious inflammatory lesions were observed in lung tissues of ALI mice. Overexpression of miR-135a-5p or TBK1 knockdown remarkably decreased IL-1β, IL-6, and TNF-α serum concentrations and increased IL-10 level within lung tissues. Activated NRF2/TXNIP pathway and oxidative stress were additionally found within ALI murines, which were regulated by miR-315a-5p and TBK1. Further research revealed that miR-135a-5p negatively regulated TBK1 expression to mediate proinflammatory response and oxidative stress.

Conclusion: miR-135a-5p targeted TBK1 to regulate inflammatory/oxidative stress responses in ALI. Such results might bring a new potential target for ALI treatment.

Publication types

  • Retracted Publication

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / genetics
  • Acute Lung Injury* / metabolism
  • Animals
  • Antioxidants
  • Carrier Proteins
  • Lipopolysaccharides
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-E2-Related Factor 2 / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Thioredoxins / metabolism

Substances

  • Antioxidants
  • Carrier Proteins
  • Lipopolysaccharides
  • MicroRNAs
  • NF-E2-Related Factor 2
  • Txnip protein, mouse
  • Thioredoxins
  • Tbk1 protein, mouse
  • Protein Serine-Threonine Kinases