Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_DE99756211BD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration.
Périodique
Journal of Cell Science
Auteur(s)
Deák F., Mátés L., Korpos E., Zvara A., Szénási T., Kiricsi M., Mendler L., Keller-Pintér A., Ozsvári B., Juhász H., Sorokin L., Dux L., Mermod N., Puskás L.G., Kiss I.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Statut éditorial
Publié
Date de publication
2014
Volume
127
Numéro
Pt 15
Pages
3240-3256
Langue
anglais
Résumé
Here, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the expression of the Cdk inhibitor p21 and of the myogenic genes Nfix, MyoD and Myog, explaining the retarded cell cycle exit and myoblast differentiation. Rescue of Matn2 expression restored differentiation and the expression of p21 and of the myogenic genes. TGF-β1 inhibited myogenic differentiation at least in part by repressing Matn2 expression, which inhibited the onset of a positive-feedback loop whereby Matn2 and Nfix activate the expression of one another and activate myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle regeneration was delayed in Matn2(-/-) relative to wild-type mice. The expression levels of Trf3 and myogenic genes were robustly reduced in Matn2(-/-) fetal limbs and in differentiating primary myoblast cultures, establishing Matn2 as a key modulator of the regulatory cascade that initiates terminal myogenic differentiation. Our data thus identify Matn2 as a crucial component of a genetic switch that modulates the onset of tissue repair.
Mots-clé
Muscle regeneration, Myogenesis, Matn2 shRNA, TGF-beta signaling, BMP signaling, NFI, Trf3
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/12/2014 14:24
Dernière modification de la notice
20/08/2019 16:03
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