Annexin A1 drives macrophage skewing to accelerate muscle regeneration through AMPK activation.
Homeostasis
Inflammation
Macrophages
Muscle Biology
Protein kinases
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
02 03 2020
02 03 2020
Historique:
received:
02
10
2018
accepted:
21
11
2019
pubmed:
6
2
2020
medline:
4
11
2020
entrez:
5
2
2020
Statut:
ppublish
Résumé
Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution, and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identified annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing toward a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then overexpressed in infiltrating macrophages, AnxA1 activated FPR2/ALX receptors and the downstream AMPK signaling cascade, leading to macrophage skewing, dampening of inflammation, and regeneration of muscle fibers. Mice lacking AnxA1 in all cells or only in myeloid cells displayed a defect in this reparative process. In vitro experiments recapitulated these properties, with AMPK-null macrophages lacking AnxA1-mediated polarization. Collectively, these data identified the AnxA1/FPR2/AMPK axis as an important pathway in skeletal muscle injury regeneration.
Identifiants
pubmed: 32015229
pii: 124635
doi: 10.1172/JCI124635
pmc: PMC7269594
doi:
pii:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Annexin A1
0
HSH2 protein, mouse
0
Receptors, Formyl Peptide
0
annexin A1, mouse
0
formyl peptide receptor 2, mouse
0
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1156-1167Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 086867/Z/08/Z
Pays : United Kingdom
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