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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Nature communications - 10(2019), 1 vom: 11. Okt., Seite 4659

Sprache:

Englisch

Beteiligte Personen:

Bian, Zehua [VerfasserIn]
Wang, Qiang [VerfasserIn]
Zhou, Xinyu [VerfasserIn]
Tan, Tao [VerfasserIn]
Park, Ki Ho [VerfasserIn]
Kramer, H Fritz [VerfasserIn]
McDougal, Alan [VerfasserIn]
Laping, Nicholas J [VerfasserIn]
Kumar, Sanjay [VerfasserIn]
Adesanya, T M Ayodele [VerfasserIn]
Sermersheim, Matthew [VerfasserIn]
Yi, Frank [VerfasserIn]
Wang, Xinxin [VerfasserIn]
Wu, Junwei [VerfasserIn]
Gumpper, Kristyn [VerfasserIn]
Jiang, Qiwei [VerfasserIn]
He, Duofen [VerfasserIn]
Lin, Pei-Hui [VerfasserIn]
Li, Haichang [VerfasserIn]
Guan, Fangxia [VerfasserIn]
Zhou, Jingsong [VerfasserIn]
Kohr, Mark J [VerfasserIn]
Zeng, Chunyu [VerfasserIn]
Zhu, Hua [VerfasserIn]
Ma, Jianjie [VerfasserIn]

Links:

Volltext

Themen:

Calcium
Glucose
IY9XDZ35W2
Insulin
Journal Article
MG53 protein, mouse
Membrane Proteins
Research Support, N.I.H., Extramural
SY7Q814VUP

Anmerkungen:

Date Completed 04.02.2020

Date Revised 10.01.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-019-12483-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM302117350