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 GuanJingsong Zhou, Mark J. Kohr, Chunyu Zeng, Hua Zhu, Jianjie Ma

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article number4659
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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

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