BMSC-derived exosomes alleviate smoke inhalation lung injury through blockade of the HMGB1/NF-κB pathway

Life Sci. 2020 Sep 15:257:118042. doi: 10.1016/j.lfs.2020.118042. Epub 2020 Jul 1.

Abstract

Aims: To investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomes in smoke inhalation lung injury.

Main methods: In this study, we initially isolated exosomes from BMSCs and identified them by western blot and transmission electron microscopy. BMSC-derived exosomes were then used to treat in vitro and in vivo models of smoke inhalation lung injury. Pathologic alterations in lung tissue, the levels of inflammatory factors and apoptosis-related factors, and the expression of HMGB1 and NF-κB were determined to evaluate the therapeutic effect of BMSC-derived exosomes.

Key findings: We found that BMSC-derived exosomes could alleviate the injury caused by smoke inhalation. Smoke inhalation increased the levels of inflammatory factors and apoptosis-related factors and the expression of HMGB1 and NF-κB, and these increases were reversed by BMSC-derived exosomes. HMGB1 overexpression abrogated the exosome-induced decreases in inflammatory factors, apoptosis-related factors and NF-κB.

Significance: Collectively, these results indicate that BMSC-derived exosomes can effectively alleviate smoke inhalation lung injury by inhibiting the HMGB1/NF-κB pathway, suggesting that exosome, a noncellular therapy, is a potential therapeutic strategy for inhalation lung injury.

Keywords: Exosome; HMGB1; Lung injury; Mesenchymal stem cell; Smoke inhalation.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Exosomes / metabolism*
  • HMGB1 Protein / metabolism
  • Inflammation / pathology
  • Lung Injury / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / metabolism*
  • NF-kappa B / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Smoke / adverse effects
  • Smoke Inhalation Injury / metabolism*
  • Smoke Inhalation Injury / therapy

Substances

  • HMGB1 Protein
  • NF-kappa B
  • Smoke