Long non-coding RNA TUG1 promotes airway remodeling and mucus production in asthmatic mice through the microRNA-181b/HMGB1 axis

Int Immunopharmacol. 2021 May;94:107488. doi: 10.1016/j.intimp.2021.107488. Epub 2021 Feb 26.

Abstract

MicroRNA-181b (miR-181b) has been well noted with anti-inflammatory properties in several pathological conditions. It has also been suggested to be downregulated in patients with asthma. In this study, we explored the function of miR-181b in airway remodeling in asthmatic mice and the molecular mechanism. A mouse model with asthma was induced by ovalbumin (OVA) challenge, and miR-181b was found to be downregulated in lung tissues in the OVA-challenged mice. Overexpression of miR-181b was introduced in mice, after which the respiratory resistance, inflammatory infiltration, mucus production, and epithelial-mesenchymal transition (EMT) and fibrosis in mouse airway tissues were decreased. The integrated bioinformatics analysis suggested long non-coding RNA (lncRNA) TUG1 as a sponge for miR-181b. miR-181 directly targeted high mobility group box 1 (HMGB1) mRNA. HMGB1 was suggested to enhance activation of the nuclear factor kappa B (NF-κB) signaling. Further upregulation of lncRNA TUG1 blocked the protective functions of miR-181b in asthmatic mice. To conclude, this study evidenced that lncRNA TUG1 reinforces HMGB1 expression through sequestering microRNA-181b, which activates the NF-κB signaling pathway and promotes airway remodeling in asthmatic mice. This study may provide novel ideas in asthma management.

Keywords: Asthma; HMGB1; LncRNA TUG1; NF-κB signaling pathway; miR-181b.

MeSH terms

  • Airway Remodeling / genetics
  • Airway Remodeling / immunology*
  • Allergens
  • Animals
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • HMGB1 Protein / genetics
  • HMGB1 Protein / immunology*
  • Lung / pathology
  • Mice, Inbred BALB C
  • MicroRNAs / immunology*
  • Mucus / immunology
  • NF-kappa B / immunology
  • Ovalbumin
  • RNA, Long Noncoding / immunology*
  • Signal Transduction

Substances

  • Allergens
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • MicroRNAs
  • NF-kappa B
  • RNA, Long Noncoding
  • long non-coding RNA TUG1, mouse
  • mirn181 microRNA, mouse
  • Ovalbumin