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

被引：110

作者：

Jia, Yanlin ^{[1
]}

Chen, Ken ^{[2
]}

Lin, Peihui ^{[3
,4
]}

Lieber, Gissela ^{[1
]}

Nishi, Miyuki ^{[5
]}

Yan, Rosalie ^{[6
]}

Wang, Zhen ^{[2
]}

Yao, Yonggang ^{[2
]}

Li, Yu ^{[2
]}

Whitson, Bryan A. ^{[3
]}

Duann, Pu ^{[3
]}

Li, Haichang ^{[3
]}

Zhou, Xinyu ^{[3
]}

Zhu, Hua ^{[3
,4
]}

Takeshima, Hiroshi ^{[5
]}

Hunter, John C. ^{[1
]}

McLeod, Robbie L. ^{[1
]}

Weisleder, Noah ^{[4
,6
,7
]}

Zeng, Chunyu ^{[2
]}

Ma, Jianjie ^{[3
,4
,6
]}

机构：

[1] Merck Res Lab, Dept Resp & Immunol, Kenilworth, NJ 07033 USA

[2] Third Mil Med Univ, Daping Hosp, Chongqing Inst Cardiol, Dept Cardiol, Chongqing 400042, Peoples R China

[3] Ohio State Univ, Davis Heart & Lung Res Inst, Dept Surg, Columbus, OH 43210 USA

[4] Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA

[5] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Biol Chem, Kyoto 6068501, Japan

[6] TRIM Edicine Inc, Div Prot Therapeut, North Brunswick, NJ 08854 USA

[7] Ohio State Univ, Davis Heart & Lung Res Inst, Dept Physiol & Cell Biol, Columbus, OH 43210 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

ISCHEMIA-REPERFUSION INJURY; INDUCED PULMONARY-EMPHYSEMA; CIGARETTE-SMOKE; RETINOIC ACID; MECHANISMS; MG53; DYSFERLIN; INSIGHTS; DISEASE; MUSCLE;

D O I：

10.1038/ncomms5387

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 42 条

[1] Reperfusion injury: Experimental evidence and clinical implications [J].

Ambrosio, G ;

Tritto, I .

AMERICAN HEART JOURNAL, 1999, 138 (02) :S69-S75

[2] Membrane repair and immunological danger [J].

Andrews, NW .

EMBO REPORTS, 2005, 6 (09) :826-830

[3] New concepts in reactive oxygen species and cardiovascular reperfusion physiology [J].

Becker, LB .

CARDIOVASCULAR RESEARCH, 2004, 61 (03) :461-470

[4] Effects of all-trans-retinoic acid in promoting alveolar repair [J].

Belloni, PN ;

Garvin, L ;

Mao, CP ;

Bailey-Healy, I ;

Leaffer, D .

CHEST, 2000, 117 (05) :235S-241S

[5] Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity [J].

Borzone, Gisella ;

Liberona, Leonel ;

Olmos, Pablo ;

Saez, Claudia ;

Meneses, Manuel ;

Reyes, Tatiana ;

Moreno, Rodrigo ;

Lisboa, Carmen .

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2007, 293 (03) :R1342-R1349

[6] Protective effects of hyperbaric oxygen and iloprost on ischemia/reperfusion-induced lung injury in a rabbit model [J].

Bozok, S. ;

Ilhan, G. ;

Yilmaz, Y. ;

Dokumcu, Z. ;

Tumkaya, L. ;

Karamustafa, H. ;

Karakisi, S. Ozan ;

Ergene, S. ;

Sener, E. .

EUROPEAN JOURNAL OF MEDICAL RESEARCH, 2012, 17

[7] Chronic LPS Inhalation Causes Emphysema-Like Changes in Mouse Lung that Are Associated with Apoptosis [J].

Brass, David M. ;

Hollingsworth, John W. ;

Cinque, Mark ;

Li, Zhouwei ;

Potts, Erin ;

Toloza, Eric ;

Foster, William M. ;

Schwartz, David A. .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2008, 39 (05) :584-590

[8] Membrane Repair Defects in Muscular Dystrophy Are Linked to Altered Interaction between MG53, Caveolin-3, and Dysferlin [J].

Cai, Chuanxi ;

Weisleder, Noah ;

Ko, Jae-Kyun ;

Komazaki, Shinji ;

Sunada, Yoshihide ;

Nishi, Miyuki ;

Takeshima, Hiroshi ;

Ma, Jianjie .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (23) :15894-15902

[9] MG53 Regulates Membrane Budding and Exocytosis in Muscle Cells [J].

Cai, Chuanxi ;

Masumiya, Haruko ;

Weisleder, Noah ;

Pan, Zui ;

Nishi, Miyuki ;

Komazaki, Shinji ;

Takeshima, Hiroshi ;

Ma, Jianjie .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (05) :3314-3322

[10] MG53 nucleates assembly of cell membrane repair machinery [J].

Cai, Chuanxi ;

Masumiya, Haruko ;

Weisleder, Noah ;

Matsuda, Noriyuki ;

Nishi, Miyuki ;

Hwang, Moonsun ;

Ko, Jae-Kyun ;

Lin, Peihui ;

Thornton, Angela ;

Zhao, Xiaoli ;

Pan, Zui ;

Komazaki, Shinji ;

Brotto, Marco ;

Takeshima, Hiroshi ;

Ma, Jianjie .

NATURE CELL BIOLOGY, 2009, 11 (01) :56-U108

← 1 2 3 4 5 →