Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Nature Metabolism
Gurpreet S BahtJames P White

Abstract

The immune system plays a multifunctional role throughout the regenerative process, regulating both pro-/anti-inflammatory phases and progenitor cell function. In the present study, we identify the myokine/cytokine Meteorin-like (Metrnl) as a critical regulator of muscle regeneration. Mice genetically lacking Metrnl have impaired muscle regeneration associated with a reduction in immune cell infiltration and an inability to transition towards an anti-inflammatory phenotype. Isochronic parabiosis, joining wild-type and whole-body Metrnl knock-out (KO) mice, returns Metrnl expression in the injured muscle and improves muscle repair, providing supportive evidence for Metrnl secretion from infiltrating immune cells. Macrophage-specific Metrnl KO mice are also deficient in muscle repair. During muscle regeneration, Metrnl works, in part, through Stat3 activation in macrophages, resulting in differentiation to an anti-inflammatory phenotype. With regard to myogenesis, Metrnl induces macrophage-dependent insulin-like growth factor 1 production, which has a direct effect on primary muscle satellite cell proliferation. Perturbations in this pathway inhibit efficacy of Metrnl in the regenerative process. Together, these studies identify ...Continue Reading

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Citations

Oct 2, 2020·Acta Pharmacologica Sinica·Zhu-Wei MiaoChao-Yu Miao
Jul 23, 2020·Nature Metabolism·Bénédicte Chazaud
Feb 3, 2021·Mechanisms of Ageing and Development·Akshay BarejaJames P White
Feb 27, 2021·The Journal of Experimental Medicine·Celia RupérezAnna Planavila
Mar 19, 2021·Immunometabolism·Joel D Schilling
Mar 28, 2021·Npj Regenerative Medicine·Anselmo MoriscotT Scott Bowen
May 1, 2021·International Journal of Molecular Sciences·Jan FrohlichManlio Vinciguerra
Jun 19, 2021·Seminars in Cell & Developmental Biology·Georgiana Panci, Bénédicte Chazaud
Jun 30, 2021·Seminars in Cell & Developmental Biology·Gaëtan Juban
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Aug 31, 2021·Frontiers in Physiology·Aurel B LeuchtmannChristoph Handschin

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Methods Mentioned

BETA
RNA-seq
ELISA
flow cytometry
Drop-seq
PCR
light microscopy
biopsies

Software Mentioned

Cellomics ArrayScan
Image J
Metrnl
Genomics Cell Ranger
10X
GraphPad Prism
Seurat

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