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Article Dans Une Revue Journal of Autoimmunity Année : 2021

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

Résumé

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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Dates et versions

hal-03655547 , version 1 (24-05-2023)

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Paternité - Pas d'utilisation commerciale

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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, 2021, 121, pp.102660. ⟨10.1016/j.jaut.2021.102660⟩. ⟨hal-03655547⟩
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