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Poster De Conférence Année : 2020

Targeting aldehyde dehydrogenase to mitigate the physiopathology of Duchenne muscular dystrophy

Résumé

Skeletal muscle contains cell populations displaying aldehyde dehydrogenase (ALDH) activity that confers proliferation, aldehyde detoxification, and survival capacities, and produces essential metabolites, such as retinoic acid. We previously distinguished two progenitor cell populations based on the expression of the extracellular marker CD34: ALDH+CD34- cells engage in a myogenic program in vitro and in vivo while ALDH+CD34+ cells differentiate towards a mesenchymal program (i.e., osteogenic, chondrogenic, and adipose tissue). ALDH+ cells could be used for cell therapy, mandating more characterization in healthy and dystrophic tissues. Here, we investigated the presence and characteristics of total ALDH+ cells and the expression of the 19 ALDH isoenzymes in aging and Duchenne muscular dystrophy (DMD) skeletal muscles using the complementary methods of flow cytometry, immunofluorescence, and quantitative reverse-transcription polymerase chain reaction. In Humans (n=50), we found no influence of age (28-93 years old) and sex (25 women, 25 men) on the number of ALDH+ cells. In contrast, DMD was associated with a significant increase in total ALDH+ cells in both human patients' skeletal muscle and dog models. This increase was mostly driven by the non-myogenic ALDH+CD34+ subpopulation and corresponded to increased interstitial cells expressing the isoenzymes ALDH1L1, ALDH3A2, and ALDH9A1. Our study suggests a pivotal role for ALDH metabolism in muscle, depending on which isoenzymes are expressed. ALDH1A1, mostly expressed in healthy tissue and involved in the retinoic acid pathway, could contribute to homeostasis, while ALDH1L1, ALDH3A2, and ALDH9A1 could participate in or result from the remodeling in dystrophic muscle (e.g., fibrosis, inflammation, and adipose tissue expansion). (Etienne et al., JCSM 2020; 11:1047-1069).
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Dates et versions

hal-03440309 , version 1 (22-11-2021)

Identifiants

  • HAL Id : hal-03440309 , version 1

Citer

Jessy Etienne, Pierre Joanne, Cyril Catelain, Stéphanie Riveron, Alexandra Clarissa Bayer, et al.. Targeting aldehyde dehydrogenase to mitigate the physiopathology of Duchenne muscular dystrophy. 3rd Victorian Muscle Network Symposium 2020, Oct 2020, Virtual Congress, Australia. ⟨hal-03440309⟩
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