Exosomes derived from adipose tissue-derived stem cells alleviated H 2 O 2 -induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway.

Autor: Li Y; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China., Xiao Y; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China., Shang Y; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China., Xu C; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China., Han C; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China., Hu D; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China. hudhai6322@163.com., Han J; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China. hanjuntao70@163.com., Wang H; Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, 127 West Chang-Le Road, Xi'an, 710032, Shaanxi, China. wanght@fmmu.edu.cn.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2024 May 25; Vol. 40 (1), pp. 39. Date of Electronic Publication: 2024 May 25.
DOI: 10.1007/s10565-024-09881-6
Abstrakt: Hypertrophic scar (HS) is characterized by excessive collagen deposition and myofibroblasts activation. Endothelial-to-mesenchymal transition (EndoMT) and oxidative stress were pivotal in skin fibrosis process. Exosomes derived from adipose tissue-derived stem cells (ADSC-Exo) have the potential to attenuate EndoMT and inhibit fibrosis. The study revealed reactive oxygen species (ROS) levels were increased during EndoMT occurrence of dermal vasculature of HS. The morphology of endothelial cells exposure to H 2 O 2, serving as an in vitro model of oxidative stress damage, transitioned from a cobblestone-like appearance to a spindle-like shape. Additionally, the levels of endothelial markers decreased in H 2 O 2 -treated endothelial cell, while the expression of fibrotic markers increased. Furthermore, H 2 O 2 facilitated the accumulation of ROS, inhibited cell proliferation, retarded its migration and suppressed tube formation in endothelial cell. However, ADSC-Exo counteracted the biological effects induced by H 2 O 2 . Subsequently, miRNAs sequencing analysis revealed the significance of mir-486-3p in endothelial cell exposed to H 2 O 2 and ADSC-Exo. Mir-486-3p overexpression enhanced the acceleration of EndoMT, its inhibitors represented the attenuation of EndoMT. Meanwhile, the target regulatory relationship was observed between mir-486-3p and Sirt6, whereby Sirt6 exerted its anti-EndoMT effect through Smad2/3 signaling pathway. Besides, our research had successfully demonstrated the impact of ADSC-Exo and mir-486-3p on animal models. These findings of our study collectively elucidated that ADSC-Exo effectively alleviated H 2 O 2 -induced ROS and EndoMT by inhibiting the mir-486-3p/Sirt6/Smad axis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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