Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle
Articolo
Data di Pubblicazione:
2016
Citazione:
Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle / A. Farini, C. Sitzia, L. Cassinelli, F. Colleoni, D. Parolini, U. Giovanella, S. Maciotta, A. Colombo, M. Meregalli, Y. Torrente. - In: DEVELOPMENT. - ISSN 0950-1991. - 143:4(2016 Feb), pp. 658-669. [10.1242/dev.126193]
Abstract:
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle wasting and premature death. The defective gene is dystrophin, a structural protein, absence of which causes membrane fragility and myofiber necrosis. Several lines of evidence showed that in adult DMD patients dystrophin is involved in signaling pathways that regulate calcium homeostasis and differentiation programs. However, secondary aspects of the disease, such as inflammation and fibrosis development, might represent a bias in the analysis. Because fetal muscle is not influenced by gravity and does not suffer from mechanical load and/or inflammation, we investigated 12-week-old fetal DMD skeletal muscles, highlighting for the first time early alterations in signaling pathways mediated by the absence of dystrophin itself. We found that PLC/IP3/IP3R/Ryr1/Ca2+ signaling is widely active in fetal DMD skeletal muscles and, through the calcium-dependent PKCa protein, exerts a fundamental regulatory role in delaying myogenesis and in myofiber commitment. These data provide new insights into the origin of DMD pathology during muscle development.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
DMD fetus; Dystrophin signaling; Calcium channels; IP3/IP3R pathway; Myosin isoforms
Elenco autori:
A. Farini, C. Sitzia, L. Cassinelli, F. Colleoni, D. Parolini, U. Giovanella, S. Maciotta, A. Colombo, M. Meregalli, Y. Torrente
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