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

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...

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Bibliographic Details
Published in:Nature communications 2014-07, Vol.5 (1), p.4387-4387, Article 4387
Main Authors: Jia, Yanlin, Chen, Ken, Lin, Peihui, Lieber, Gissela, Nishi, Miyuki, Yan, Rosalie, Wang, Zhen, Yao, Yonggang, Li, Yu, Whitson, Bryan A, Duann, Pu, Li, Haichang, Zhou, Xinyu, Zhu, Hua, Takeshima, Hiroshi, Hunter, John C, McLeod, Robbie L, Weisleder, Noah, Zeng, Chunyu, Ma, Jianjie
Format: Article
Language:English
Subjects:
Acute Lung Injury - drug therapy
Acute Lung Injury - genetics
Acute Lung Injury - pathology
Animals
Cardiology
Carrier Proteins - administration & dosage
Carrier Proteins - genetics
Carrier Proteins - metabolism
Carrier Proteins - pharmacology
Cell Hypoxia - drug effects
Cell Membrane - drug effects
Cell Membrane - metabolism
Cells
Cells, Cultured
Disease Models, Animal
Edema
Epithelial Cells - drug effects
Epithelial Cells - pathology
Female
Humans
Lung - pathology
Lung diseases
Male
Mice, Knockout
Molecular Targeted Therapy - methods
Musculoskeletal system
Physiology
Proteins
Rats
Rats, Sprague-Dawley
Rats, Wistar
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Reperfusion Injury - drug therapy
Reperfusion Injury - pathology
Respiration, Artificial - adverse effects
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Summary: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms5387