Exosome miR-223-3p in the bone marrow-derived mesenchymal stem cells alleviates the inflammation and airway remodeling through NLRP3-induced ASC/Caspase-1/GSDMD signaling pathway

Int Immunopharmacol. 2023 Oct:123:110746. doi: 10.1016/j.intimp.2023.110746. Epub 2023 Aug 5.

Abstract

Asthma is one of the most common chronic respiratory diseases in the world. Exploration and understanding of the pathogenesis of epithelial-mesenchymal transition in airway epithelial cells, and the development of new molecular drugs targeted at airway inflammation and remodeling have become the key and hot points in the prevention and treatment of asthma. Emerging evidence has proven that miRNAs are strongly associated with numerous chronic respiratory diseases including asthma, but the involved molecular mechanisms have not been revealed. In the present study, we successfully isolated exosomes from BMMSCs and found that the derived exosomes could improve airway inflammation and remodeling in ovalbumin-induced asthma rats. Furthermore, we found that the highly expressed miR-223-3p in exosomes might play a key pivotal role in the protective effects on airway remodeling and asthma by regulating the NLRP3-induced ASC/Caspase-1/GSDMD signaling pathway. These results provided a promising molecule candidate and target for the therapy of asthma.

Keywords: Airway remodeling; Asthma; Exosomes; Inflammation; NLRP3 signaling pathway; miRNAs.

MeSH terms

  • Airway Remodeling
  • Animals
  • Asthma* / drug therapy
  • Bone Marrow / pathology
  • Caspase 1 / metabolism
  • Caspases / metabolism
  • Exosomes* / metabolism
  • Inflammation
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • Rats
  • Signal Transduction

Substances

  • Caspase 1
  • Caspases
  • MicroRNAs
  • MIRN223 microRNA, rat
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Gsdmd protein, rat
  • Pycard protein, rat
  • Nlrp3 protein, rat