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Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle.
- Source :
-
Development (Cambridge, England) [Development] 2016 Feb 15; Vol. 143 (4), pp. 658-69. - Publication Year :
- 2016
-
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/Ca(2+) signaling is widely active in fetal DMD skeletal muscles and, through the calcium-dependent PKCĪ± 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.<br /> (© 2016. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Biomarkers metabolism
Biopsy
Calcium metabolism
Calcium Channels metabolism
Fetus pathology
Gene Expression Regulation, Developmental
Mice, Inbred C57BL
Mice, Inbred mdx
Models, Biological
Muscle Fibers, Skeletal metabolism
Muscle Fibers, Skeletal pathology
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Muscular Dystrophy, Animal metabolism
Muscular Dystrophy, Animal pathology
Muscular Dystrophy, Duchenne pathology
PAX7 Transcription Factor metabolism
Protein Kinase C-alpha metabolism
Calcium Signaling
Fetus metabolism
Inositol 1,4,5-Trisphosphate metabolism
Muscle Development
Muscle, Skeletal embryology
Muscular Dystrophy, Duchenne embryology
Muscular Dystrophy, Duchenne metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 143
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 26884398
- Full Text :
- https://doi.org/10.1242/dev.126193