Sustained elevation of MG53 in the bloodstream increases tissue regenerative capacity without compromising metabolic function

Zehua Bian, Qiang Wang, Xinyu Zhou, Tao Tan, Ki Ho Park, H. Fritz Kramer, Alan McDougal, Nicholas J. Laping, Sanjay Kumar, T. M. Ayodele Adesanya, Matthew Sermersheim, Frank Yi, Xinxin Wang, Junwei Wu, Kristyn Gumpper, Qiwei Jiang, Duofen He, Pei-Hui Lin, Haichang Li, Fangxia Guan, Jingsong Zhou, Mark J. Kohr, Chunyu Zeng, Hua Zhu () and Jianjie Ma ()
Additional contact information
Zehua Bian: The Ohio State University
Qiang Wang: The Ohio State University
Xinyu Zhou: The Ohio State University
Tao Tan: The Ohio State University
Ki Ho Park: The Ohio State University
H. Fritz Kramer: GlaxoSmithKline, Inc.
Alan McDougal: GlaxoSmithKline, Inc.
Nicholas J. Laping: Novel Human Genetics Research Unit, GlaxoSmithKline, Inc.
Sanjay Kumar: Novel Human Genetics Research Unit, GlaxoSmithKline, Inc.
T. M. Ayodele Adesanya: The Ohio State University
Matthew Sermersheim: The Ohio State University
Frank Yi: The Ohio State University
Xinxin Wang: The First Affiliated Hospital of Zhengzhou University
Junwei Wu: The First Affiliated Hospital of Zhengzhou University
Kristyn Gumpper: The Ohio State University
Qiwei Jiang: The Ohio State University
Duofen He: The Third Military Medical University
Pei-Hui Lin: The Ohio State University
Haichang Li: The Ohio State University
Fangxia Guan: School of Life Sciences, Zhengzhou University
Jingsong Zhou: University of Texas at Arlington
Mark J. Kohr: Johns Hopkins University
Chunyu Zeng: The Third Military Medical University
Hua Zhu: The Ohio State University
Jianjie Ma: The Ohio State University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body.

Date: 2019
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DOI: 10.1038/s41467-019-12483-0

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