Abstract
Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors.
Highlights
Skeletal muscles comprise 40–50% of the total adult human body mass and are responsible for a number of functions including force generation, movement and body support
They include Duchenne muscular dystrophy (DMD) which is characterized by rapidly progressive muscle degeneration primary caused by lack of dystrophin, and sarcopenia which refers to the irreversible decline of skeletal muscle mass, strength, and function with age [4]
Samples from 4 DMD and 4 AGE skeletal muscle tissues were analyzed by hybridization against control samples
Summary
Skeletal muscles comprise 40–50% of the total adult human body mass and are responsible for a number of functions including force generation, movement and body support. At the single muscle fiber level, sarcopenia was associated to hallmarks of morphological apoptosis, decline in protein synthesis increased DNA, protein and lipid oxidation, accumulation of mitochondrial abnormalities and calcium dyshomeostasis [10,11,12,13,14]. Taken together, these data suggest that common remodeling process occurred in both pathological and aging atrophying conditions and that it may be related to transcriptional alterations affecting numerous molecular pathways and biological functions, modifying tissue and morphological characteristics of the muscle. The observed patterns could be regulated by common transcription factors (TFs) to be identified
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
