microRNA-149-5p mediates the PM2.5-induced inflammatory response by targeting TAB2 via MAPK and NF-κB signaling pathways in vivo and in vitro

Cell Biol Toxicol. 2023 Jun;39(3):703-717. doi: 10.1007/s10565-021-09638-5. Epub 2021 Jul 31.


Epidemiological evidence has shown that fine particulate matter (PM2.5)-triggered inflammatory cascades are pivotal causes of chronic obstructive pulmonary disease (COPD). However, the specific molecular mechanism involved in PM2.5-induced COPD has not been clarified. Herein, we found that PM2.5 significantly downregulated miR-149-5p and activated the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and generated the inflammatory response in COPD mice and in human bronchial epithelial (BEAS-2B) cells. We determined that increased expression of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) induced by PM2.5 was associated with decreased expression of miR-149-5p. The loss- and gain-of-function approach further confirmed that miR-149-5p could inhibit PM2.5-induced cell inflammation in BEAS-2B cells. The double luciferase reporter assay showed that miR-149-5p directly targeted TGF-beta-activated kinase 1 binding protein 2 (TAB2), which regulates the MAPK and NF-κB signaling pathways. We showed that miR-149-5p mediated the inflammatory response by targeting the 3'-UTR sequence of TAB2 and that it subsequently weakened the TAB2 promotor effect via the MAPK and NF-κB signaling pathways in BEAS-2B cells exposed to PM2.5. Thus, miR-149-5p may be a key factor in PM2.5-induced COPD. This study improves our understanding of the molecular mechanism of COPD.

Keywords: COPD; Inflammatory response; PM2.5; TAB2; miR-149-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Particulate Matter / toxicity
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Signal Transduction


  • NF-kappa B
  • Mitogen-Activated Protein Kinases
  • MicroRNAs
  • Particulate Matter
  • TAB2 protein, human
  • Adaptor Proteins, Signal Transducing
  • MIRN149 microRNA, human