Loss of ARNT in skeletal muscle limits muscle regeneration in aging.
aging
hypoxia signaling
muscle regeneration
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
04
04
2020
revised:
23
09
2020
accepted:
28
09
2020
pubmed:
17
10
2020
medline:
24
4
2021
entrez:
16
10
2020
Statut:
ppublish
Résumé
The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.
Identifiants
pubmed: 33064329
doi: 10.1096/fj.202000761RR
pmc: PMC7756517
doi:
Substances chimiques
Arnt protein, mouse
0
Aryl Hydrocarbon Receptor Nuclear Translocator
138391-32-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16086-16104Subventions
Organisme : NIA NIH HHS
ID : K76 AG059996
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007260
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : HHS | NIH | National Institute on Aging (NIA)
ID : P30AG031679
Informations de copyright
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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