Exosomes derived from adipose tissue-derived stem cells alleviated H2O2-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

作者：Yan Li, Yujie Xiao, Yage Shang, Chaolei Xu, Chao Han, Dahai Hu, Juntao Han, Hongtao Wang · 发表于：Cell Biology and Toxicology · 年份：2024 · DOI：10.1007/s10565-024-09881-6 · 被引用次数：13 · 研究领域：Dermatologic Treatments and Research、Diagnosis and Treatment of Venous Diseases、Systemic Sclerosis and Related Diseases

Abstract 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 successfu...