MG53 attenuates nitrogen mustard-induced acute lung injury.
MG53
acute lung injury
nitrogen mustard
oxidative stress
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
24
07
2021
received:
28
05
2021
accepted:
01
09
2021
pubmed:
25
2
2022
medline:
8
4
2022
entrez:
24
2
2022
Statut:
ppublish
Résumé
Nitrogen mustard (NM) is an alkylating vesicant that causes severe pulmonary injury. Currently, there are no effective means to counteract vesicant-induced lung injury. MG53 is a vital component of cell membrane repair and lung protection. Here, we show that mice with ablation of MG53 are more susceptible to NM-induced lung injury than the wild-type mice. Treatment of wild-type mice with exogenous recombinant human MG53 (rhMG53) protein ameliorates NM-induced lung injury by restoring arterial blood oxygen level, by improving dynamic lung compliance and by reducing airway resistance. Exposure of lung epithelial and endothelial cells to NM leads to intracellular oxidative stress that compromises the intrinsic cell membrane repair function of MG53. Exogenous rhMG53 protein applied to the culture medium protects lung epithelial and endothelial cells from NM-induced membrane injury and oxidative stress, and enhances survival of the cells. Additionally, we show that loss of MG53 leads to increased vulnerability of macrophages to vesicant-induced cell death. Overall, these findings support the therapeutic potential of rhMG53 to counteract vesicant-induced lung injury.
Identifiants
pubmed: 35199443
doi: 10.1111/jcmm.16917
pmc: PMC8980905
doi:
Substances chimiques
MG53 protein, mouse
0
Membrane Proteins
0
Recombinant Proteins
0
Mechlorethamine
50D9XSG0VR
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1886-1895Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL137090
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070752
Pays : United States
Organisme : Ohio State University
Organisme : Department of Defense
ID : W81XWH1810787
Organisme : NIA NIH HHS
ID : R01 AG056919
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL143000
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106394
Pays : United States
Informations de copyright
© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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