HSF1 enhances the attenuation of exosomes from mesenchymal stem cells to hemorrhagic shock induced lung injury by altering the protein profile of exosomes

Int Immunopharmacol. 2023 Oct:123:110693. doi: 10.1016/j.intimp.2023.110693. Epub 2023 Jul 26.


Severe hemorrhagic shock (HS) leads to lung injury, resulting in respiratory insufficiency. Mesenchymal stem cell (MSC)-derived exosomes have therapeutic effects on the organ injury. HSF1 has been reported to protect the lung against injury. In this study, the role of exosomes from HSF1-overexpressed MSCs (HSF1-EVs) in HS-induced lung injury was investigated. We constructed a mouse model of lung injury by induction with HS and pre-treated it with HSF1-EVs. It was clarified that HSF1-EVs manifested better protective effects on HS-induced lung injury compared with the exosomes derived from control MSCs. Inhalation of HSF1-EVs declined the ratio of wet to dry and total protein concentration in bronchoalveolar lavage fluids. Besides, HSF1-EVs greatly inhibited the production of inflammatory cytokines (IL-1β, IL-6, MCP-1 and HMGB1), and constrained the pulmonary neutrophilic infiltration induced by HS. A reduction of oxidative stress was observed in HSF1-EV-treated mice. HSF1-EVs suppressed the HS-induced apoptosis of lung cell and downregulated Bcl-2 expression, while promoting Bax expression. The key proteins of pulmonary epithelial barrier, E-cadherin, ZO-1 and Occludin, were all upregulated in HS-treated mice after HSF1-EV inhalation, suggesting that HSF1-EVs played a protective role in the epithelial barrier of lung. Additionally, the results of proteomics showed that HSF1 overexpression altered the protein profile of MSC-derived exosomes, which might explain the more significant relief effect of HSF1-EVs on lung injury compared with that of Plasmid-EVs. These new findings demonstrated that the exosomes secreted by HSF1-overexpressed MSCs can be an effective precautionary measure for lung injury induced by HS.

Keywords: Exosomes; HSF1; Hemorrhagic shock; Lung injury; Proteomic.

MeSH terms

  • Animals
  • Exosomes* / metabolism
  • Heat Shock Transcription Factors / metabolism
  • Lung / metabolism
  • Lung Injury* / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Shock, Hemorrhagic* / therapy


  • Hsf1 protein, mouse
  • Heat Shock Transcription Factors