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Nat Commun. 2014 Jul 18;5:4387. doi: 10.1038/ncomms5387.

Treatment of acute lung injury by targeting MG53-mediated cell membrane repair.

Author information

1
Respiratory and Immunology, Merck Research Lab, Kenilworth, NJ 07033.
2
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China 400042.
3
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
4
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854.
5
Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan.
6
Division of Protein Therapeutics, TRIM-edicine, Inc., North Brunswick, NJ 08854.
7
Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
#
Contributed equally

Abstract

Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischaemia-reperfusion and overventilation-induced injury to the lung when compared with wild-type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases.

PMID:
25034454
PMCID:
PMC4109002
DOI:
10.1038/ncomms5387
[Indexed for MEDLINE]
Free PMC Article

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