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Laminin-α2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanisms.
- Source :
-
Life science alliance [Life Sci Alliance] 2024 Oct 08; Vol. 7 (12). Date of Electronic Publication: 2024 Oct 08 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- LAMA2, coding for the laminin-α2 chain, is a crucial ECM component, particularly abundant in skeletal muscle. Mutations in LAMA2 trigger the often-lethal LAMA2 -congenital muscular dystrophy (LAMA2-CMD). Various phenotypes have been linked to LAMA2-CMD; nevertheless, the precise mechanisms that malfunction during disease onset in utero remain unknown. We generated Lama2 -deficient C2C12 cells and found that Lama2 -deficient myoblasts display proliferation, differentiation, and fusion defects, DNA damage, oxidative stress, and mitochondrial dysfunction. Moreover, fetal myoblasts isolated from the dy <superscript> W </superscript> mouse model of LAMA2-CMD display impaired differentiation and fusion in vitro. We also showed that disease onset during fetal development is characterized by a significant down-regulation of gene expression in muscle fibers, causing pronounced effects on cytoskeletal organization, muscle differentiation, and altered DNA repair and oxidative stress responses. Together, our findings provide unique insights into the critical importance of the laminin-α2 chain for muscle differentiation and muscle cell homeostasis.<br /> (© 2024 Martins et al.)
- Subjects :
- Animals
Mice
DNA Damage
Muscular Dystrophies metabolism
Muscular Dystrophies genetics
Muscular Dystrophies pathology
Cell Proliferation genetics
Cell Line
Muscle Development genetics
Disease Models, Animal
Mutation
Muscle Fibers, Skeletal metabolism
Laminin metabolism
Laminin genetics
Laminin deficiency
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Cell Differentiation genetics
Myoblasts metabolism
Oxidative Stress genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2575-1077
- Volume :
- 7
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Life science alliance
- Publication Type :
- Academic Journal
- Accession number :
- 39379105
- Full Text :
- https://doi.org/10.26508/lsa.202402829