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Mesenchymal stromal cells-derived extracellular vesicles alleviate systemic sclerosis via miR-29a-3p

Abstract : Systemic sclerosis (SSc) is a potentially lethal disease with no curative treatment. Mesenchymal stromal cells (MSCs) have proved efficacy in SSc but no data is available on MSC-derived extracellular vesicles (EVs) in this multi-organ fibrosis disease. Small size (ssEVs) and large size EVs (lsEVs) were isolated from murine MSCs or human adipose tissue-derived MSCs (ASCs). Control antagomiR (Ct) or antagomiR-29a-3p (A29a) were transfected in MSCs and ASCs before EV production. EVs were injected in the HOCl-induced SSc model at day 21 and euthanasized at day 42. We found that both ssEVs and lsEVs were effective to slow-down the course of the disease. All disease parameters improved in skin and lungs. Interestingly, down-regulating miR-29a-3p in MSCs totally abolished therapeutic efficacy. Besides, we demonstrated a similar efficacy of human ASC-EVs and importantly, EVs from A29a-transfected ASCs failed to improve skin fibrosis. We identified Dnmt3a, Pdgfrbb, Bcl2, Bcl-xl as target genes of miR-29a-3p whose regulation was associated with skin fibrosis improvement. Our study highlights the therapeutic role of miR-29a-3p in SSc and the importance of regulating methylation and apoptosis.
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Contributeur : Nathalie Salvy-Córdoba Connectez-vous pour contacter le contributeur
Soumis le : vendredi 29 avril 2022 - 16:16:57
Dernière modification le : lundi 16 mai 2022 - 17:44:28




Pauline Rozier, Marie Maumus, Alexandre Thibault Jacques Maria, Karine Toupet, Joséphine Lai-Kee-Him, et al.. Mesenchymal stromal cells-derived extracellular vesicles alleviate systemic sclerosis via miR-29a-3p. Journal of Autoimmunity, Elsevier, 2021, 121, pp.102660. ⟨10.1016/j.jaut.2021.102660⟩. ⟨hal-03655547⟩



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