Hypoxia enhances human myoblast differentiation: involvement of HIF1α and impact of DUX4, the FSHD causal gene.
Journal
Skeletal muscle
ISSN: 2044-5040
Titre abrégé: Skelet Muscle
Pays: England
ID NLM: 101561193
Informations de publication
Date de publication:
16 12 2023
16 12 2023
Historique:
received:
19
12
2022
accepted:
20
10
2023
medline:
19
12
2023
pubmed:
17
12
2023
entrez:
16
12
2023
Statut:
epublish
Résumé
Hypoxia is known to modify skeletal muscle biological functions and muscle regeneration. However, the mechanisms underlying the effects of hypoxia on human myoblast differentiation remain unclear. The hypoxic response pathway is of particular interest in patients with hereditary muscular dystrophies since many present respiratory impairment and muscle regeneration defects. For example, an altered hypoxia response characterizes the muscles of patients with facioscapulohumeral dystrophy (FSHD). We examined the impact of hypoxia on the differentiation of human immortalized myoblasts (LHCN-M2) cultured in normoxia (PO We found that the hypoxic response did not impact myoblast proliferation but activated precocious myogenic differentiation and that HIF1α was critical for this process. Hypoxia also enhanced the late differentiation of human myocytes, but in an HIF1α-independent manner. Interestingly, the impact of hypoxia on muscle cell proliferation was influenced by dexamethasone. In the FSHD pathological context, DUX4 suppressed HIF1α-mediated precocious muscle differentiation. Hypoxia stimulates myogenic differentiation in healthy myoblasts, with HIF1α-dependent early steps. In FSHD, DUX4-HIF1α interplay indicates a novel mechanism by which DUX4 could interfere with HIF1α function in the myogenic program and therefore with FSHD muscle performance and regeneration.
Sections du résumé
BACKGROUND
Hypoxia is known to modify skeletal muscle biological functions and muscle regeneration. However, the mechanisms underlying the effects of hypoxia on human myoblast differentiation remain unclear. The hypoxic response pathway is of particular interest in patients with hereditary muscular dystrophies since many present respiratory impairment and muscle regeneration defects. For example, an altered hypoxia response characterizes the muscles of patients with facioscapulohumeral dystrophy (FSHD).
METHODS
We examined the impact of hypoxia on the differentiation of human immortalized myoblasts (LHCN-M2) cultured in normoxia (PO
RESULTS
We found that the hypoxic response did not impact myoblast proliferation but activated precocious myogenic differentiation and that HIF1α was critical for this process. Hypoxia also enhanced the late differentiation of human myocytes, but in an HIF1α-independent manner. Interestingly, the impact of hypoxia on muscle cell proliferation was influenced by dexamethasone. In the FSHD pathological context, DUX4 suppressed HIF1α-mediated precocious muscle differentiation.
CONCLUSION
Hypoxia stimulates myogenic differentiation in healthy myoblasts, with HIF1α-dependent early steps. In FSHD, DUX4-HIF1α interplay indicates a novel mechanism by which DUX4 could interfere with HIF1α function in the myogenic program and therefore with FSHD muscle performance and regeneration.
Identifiants
pubmed: 38104132
doi: 10.1186/s13395-023-00330-2
pii: 10.1186/s13395-023-00330-2
pmc: PMC10724930
doi:
Substances chimiques
Homeodomain Proteins
0
DUX4L1 protein, human
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21Subventions
Organisme : Medical Research Council
ID : MR/X001520/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P023215/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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