Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration
Here we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling early steps of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Matn2 silencing delayed...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2014
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| Sorozat: | JOURNAL OF CELL SCIENCE
127 No. 15 |
| doi: | 10.1242/jcs.141556 |
| mtmt: | 2701856 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/13608 |
| Tartalmi kivonat: | Here we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling early steps of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Matn2 silencing delayed expression of the Cdk inhibitor p21 and of the Nfix, MyoD, Myog myogenic genes, explaining the retarded cell cycle exit and myoblast differentiation. Matn2 expression rescue restored differentiation and the expression of p21 and of the myogenic genes. TGF-beta1 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 each other's expression as well as myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle regeneration was delayed in Matn2-/- relative to wild-type mice. Trf3 and myogenic gene expression levels robustly dropped 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 critical component of a genetic switch that modulates tissue repair onset. |
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| Terjedelem/Fizikai jellemzők: | 3240-3256 |
| ISSN: | 0021-9533 |