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Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Millennium Institute for Fundamental and Applied Biology, Pontificia Universidad Católica de Chile, Santiago, Chile
Transcription of specific skeletal
muscle genes requires the expression of the muscle regulatory factor
myogenin. To assess the role of the extracellular matrix (ECM) in
skeletal muscle differentiation, the specific inhibitors of
proteoglycan synthesis, sodium chlorate and
-D-xyloside,
were used. Treatment of cultured skeletal muscle cells with each
inhibitor substantially abolished the expression of creatine kinase and
-dystroglycan. This inhibition was totally reversed by the addition
of exogenous ECM. Myoblast treatment with each inhibitor affected the
deposition and assembly of the ECM constituents glypican, fibronectin,
and laminin. These treatments did not affect MyoD, MEF2A, and myogenin
expression and nuclear localization. Differentiated myoblast treatment
with RGDS peptides completely inhibited myogenesis without affecting the expression or nuclear localization of myogenin. Integrin-mediated signaling of focal adhesion kinase was partially inhibited by chlorate
and
-D-xyloside, an effect reversed by the addition of
exogenous ECM gel. These results suggested that the expression of
myogenin is not sufficient to successfully drive skeletal muscle formation and that ECM is required to complete the skeletal muscle differentiation process.
myogenin; proteoglycans; extracellular matrix; proteoglycan inhibitors; satellite cells
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