Mechanism of miR-130b-3p in relieving airway inflammation in asthma through HMGB1-TLR4-DRP1 axis

Cell Mol Life Sci. 2024 Dec 20;82(1):9. doi: 10.1007/s00018-024-05529-0.

Abstract

Asthma is a chronic inflammatory respiratory disease characterized by recurrent breathing difficulties caused by airway obstruction and hypersensitivity. Although there is diversity in their specific mechanisms, microRNAs (miRNAs) have a significant impact on the development of asthma. Currently, the contribution of miR-130b-3p to asthma remains elusive. The goal of this study was to examine whether miR-130b-3p attenuates house dust mite (HDM)-induced asthma through High-mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/mitochondrial fission protein (DRP1) signaling pathway. We elucidate that miR-130b-3p can bind to the HMGB1 3'UTR, attenuating HMGB1 mRNA and protein levels, and nucleo-cytoplasmic translocation of HMGB1. We observed that miR-130b-3p agomir or HMGB1 CKO attenuated HDM-induced airway inflammation and hyperresponsiveness, and decreased Th2-type cytokines in bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes. Further, HMGB1 CKO contributes to alleviating Th2 inflammation in AT-II cells (CD45.2-/CD31-/Epcam-+/proSP-C+/MHC-II+) from lung single cell suspensions of asthmatic mice by flow cytometry. Our findings identified miR-130b-3p as a potent regulator in asthma that exerts its anti-inflammatory effects by targeting HMGB1 and the subsequent HMGB1/TLR4/DRP1axis, presenting a prospective novel therapeutic avenue for asthma management.

Keywords: Asthma; HMGB1; MiR-130b-3p.

MeSH terms

  • Animals
  • Asthma* / genetics
  • Asthma* / metabolism
  • Asthma* / pathology
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Dynamins* / genetics
  • Dynamins* / metabolism
  • HMGB1 Protein* / genetics
  • HMGB1 Protein* / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pyroglyphidae / immunology
  • Signal Transduction*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Toll-Like Receptor 4* / genetics
  • Toll-Like Receptor 4* / metabolism

Substances

  • Toll-Like Receptor 4
  • MicroRNAs
  • HMGB1 Protein
  • MIRN130 microRNA, mouse
  • Tlr4 protein, mouse
  • Dynamins
  • Dnm1l protein, mouse
  • HMGB1 protein, mouse
  • Cytokines