title: Treatment of acute lung injury by targeting MG53-mediated cell membrane repair.
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.
authors.affiliation: Respiratory and Immunology, Merck Research Lab, Kenilworth, NJ 07033.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China 400042.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.|Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854.
authors.forename: Peihui
authors.initials: P
authors.lastname: Lin
authors.affiliation: Respiratory and Immunology, Merck Research Lab, Kenilworth, NJ 07033.
authors.forename: Gissela
authors.initials: G
authors.lastname: Lieber
authors.affiliation: Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Division of Protein Therapeutics, TRIM-edicine, Inc., North Brunswick, NJ 08854.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China 400042.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China 400042.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China 400042.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Whitson
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Pu
authors.initials: P
authors.lastname: Duann
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Haichang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.|Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.affiliation: Respiratory and Immunology, Merck Research Lab, Kenilworth, NJ 07033.
authors.forename: John C
authors.initials: JC
authors.lastname: Hunter
authors.affiliation: Respiratory and Immunology, Merck Research Lab, Kenilworth, NJ 07033.
authors.forename: Robbie L
authors.initials: RL
authors.lastname: McLeod
authors.affiliation: Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854.|Division of Protein Therapeutics, TRIM-edicine, Inc., North Brunswick, NJ 08854.|Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China 400042.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210.|Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854.|Division of Protein Therapeutics, TRIM-edicine, Inc., North Brunswick, NJ 08854.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D012121:Respiration, Artificial / Q000009:adverse effects; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins; C558399:TRIM72 protein, human; D000070584:Tripartite Motif Proteins