Résumé :
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This study aimed to compare the skeletal muscle response at the transcriptional level in DMD and in Aging. 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 2 chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsy samples from 4 young DMD subjects and from 4 elderly subjects were analyzed using a dedicated microarray. A group of 7 muscle biopsies from young subjects without any neuromuscular disorder was used as reference. An exhaustive meta-analysis of transcriptome data was then performed to improve the relevance of the results. Statistical analyses identified a list of 528 differentially expressed genes (out of 2,745 analyzed) of which 328 could be validated by the meta-analysis with DMD and Aging related transcriptome data. Among the 328 validated co-expressed genes, 50% were found to have the same expression profile in both groups (66 over-expressed and 88 under-expressed); these gene signatures correspond to immune/fibrosis responses and mitochondrial metabolism respectively. Generalizing these observed gene signatures by meta-analysis with large compendia of public datasets reinforced our results as they also could be identified in pathological processes (including myopathies) and in physiological conditions (including different human age-related tissues). Additionally, bioinformatic analyses enabled to identify common transcription factors that may coordinate these gene signatures. Deregulation of their expression could be responsible, at least in part, for the same transcriptome changes in both situations. This study shows that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors. The contribution of these factors in regulating gene expression is now being investigated by chromatin-immunoprecipitation experiments. This approach could be relevant in designing therapeutic strategies directed to reduce muscle atrophy.
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