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

Ferenc Deák, L. Mátés, Éva Korpos, A. Zvara, Tibor Szénási, Mónika Kiricsi, Luca Mendler, Anikó Keller-Pintér, Béla Ózsvári, Hajnalka Juhász, Lydia Sorokin, L. Dux, Nicolas Mermod, L. Puskás, I. Kiss

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3240-3256
Number of pages17
JournalJournal of Cell Science
Volume127
Issue number15
DOIs
Publication statusPublished - 2014

Fingerprint

Matrilin Proteins
Regeneration
Muscles
Myoblasts
Genes
Extracellular Matrix Proteins
Cell Cycle Checkpoints
Cell Cycle

Keywords

  • BMP signaling
  • Matn2 shRNA
  • Muscle regeneration
  • Myogenesis
  • NFI
  • TGF-β signaling
  • Trf3

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration. / Deák, Ferenc; Mátés, L.; Korpos, Éva; Zvara, A.; Szénási, Tibor; Kiricsi, Mónika; Mendler, Luca; Keller-Pintér, Anikó; Ózsvári, Béla; Juhász, Hajnalka; Sorokin, Lydia; Dux, L.; Mermod, Nicolas; Puskás, L.; Kiss, I.

In: Journal of Cell Science, Vol. 127, No. 15, 2014, p. 3240-3256.

Research output: Contribution to journalArticle

Deák, F, Mátés, L, Korpos, É, Zvara, A, Szénási, T, Kiricsi, M, Mendler, L, Keller-Pintér, A, Ózsvári, B, Juhász, H, Sorokin, L, Dux, L, Mermod, N, Puskás, L & Kiss, I 2014, 'Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration', Journal of Cell Science, vol. 127, no. 15, pp. 3240-3256. https://doi.org/10.1242/jcs.141556
Deák, Ferenc ; Mátés, L. ; Korpos, Éva ; Zvara, A. ; Szénási, Tibor ; Kiricsi, Mónika ; Mendler, Luca ; Keller-Pintér, Anikó ; Ózsvári, Béla ; Juhász, Hajnalka ; Sorokin, Lydia ; Dux, L. ; Mermod, Nicolas ; Puskás, L. ; Kiss, I. / Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration. In: Journal of Cell Science. 2014 ; Vol. 127, No. 15. pp. 3240-3256.
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