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

Yanlin Jia; Ken Chen; Peihui Lin; Gissela Lieber; Miyuki Nishi; Rosalie Yan; Zhen Wang; Yonggang Yao; Yu Li; Bryan A. Whitson; Pu Duann; Haichang Li; Xinyu Zhou; Hua Zhu; Hiroshi Takeshima; John C. Hunter; Robbie L. McLeod; Noah Weisleder; Chunyu Zeng; Jianjie Ma

doi:10.1038/ncomms5387

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

Yanlin Jia, Ken Chen, Peihui Lin, Gissela Lieber, Miyuki Nishi, Rosalie Yan, Zhen Wang, Yonggang Yao, Yu Li, Bryan A. Whitson, Pu Duann, Haichang Li, Xinyu Zhou, Hua Zhu, Hiroshi Takeshima, John C. Hunter, Robbie L. McLeod, Noah Weisleder, Chunyu Zeng, Jianjie Ma

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

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.

Original language	English
Article number	4387
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5387
State	Published - Jul 18 2014

Funding

This work was supported by grants from the National Institutes of Health (NIH) to J.M., H.T. and N.W.; (R01-AR061385 and R01-HL069000); the JSPS core-to-core program to H.T; AHA SDG grant (12SDG12070174) to H.Z; grants from the National Science Foundation of China (30925018 and 31130029) and National Basic Research Program of China (973 Program, 2013CB531104, and 2012CB517801) to C.Z.; and a Small Business Innovation Research grant from NIH awarded to TRIM-edicine, Inc.

Funders	Funder number
National Institutes of Health (NIH)	R01-AR061385
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute Family Blood Pressure Program	R01HL069000
National Heart, Lung, and Blood Institute Family Blood Pressure Program
American Historical Association	12SDG12070174
American Historical Association
Japan Society for the Promotion of Science Fund for the Promotion of Joint International Research
National Natural Science Foundation of China (NSFC)	31130029, 30925018
National Natural Science Foundation of China (NSFC)
National Basic Research Program of China (973 Program)	2013CB531104, 2012CB517801
National Basic Research Program of China (973 Program)

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms5387

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Jia, Y., Chen, K., Lin, P., Lieber, G., Nishi, M., Yan, R., Wang, Z., Yao, Y., Li, Y., Whitson, B. A., Duann, P., Li, H., Zhou, X., Zhu, H., Takeshima, H., Hunter, J. C., McLeod, R. L., Weisleder, N., Zeng, C., & Ma, J. (2014). Treatment of acute lung injury by targeting MG53-mediated cell membrane repair. Nature Communications, 5, Article 4387. https://doi.org/10.1038/ncomms5387

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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.",

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AU - Zhu, Hua

AU - Takeshima, Hiroshi

AU - Hunter, John C.

AU - McLeod, Robbie L.

AU - Weisleder, Noah

AU - Zeng, Chunyu

AU - Ma, Jianjie

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

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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