Exosomal miR-155 from M1-polarized macrophages promotes EndoMT and impairs mitochondrial function via activating NF-κB signaling pathway in vascular endothelial cells after traumatic spinal cord injury

• DOI: 10.1016/j.redox.2021.101932
• Publication Date: 2021-03-07T17:20:02Z
• Authors: Xuhui Ge; Pengyu Tang; Yuluo Rong; Dongdong Jiang; Xiao Lu; Chengyue Ji; Jiaxing Wang; Chenyu Huang; Ao Duan; Yang Liu; Xinglin Chen; Xichen Chen; Zhiyang Xu; Feng Wang; Zibin Wang; Xiaoyan Li; Wene Zhao; Jin Fan; Wei Liu; Guoyong Yin; Weihua Cai
• Keywords: Mitochondrial ROS

Pathologically, blood-spinal-cord-barrier (BSCB) disruption after spinal cord injury (SCI) leads to infiltration of numerous peripheral macrophages into injured areas and accumulation around newborn vessels. Among the leaked macrophages, M1-polarized are dominant play a crucial role throughout whole SCI process. The aim our study was investigate effects bone marrow-derived (M1-BMDMs) on vascular endothelial cells their underlying mechanism. Microvascular cell line bEnd.3 were treated with conditioned medium or exosomes derived from M1-BMDMs, followed by evaluations endothelial-to-mesenchymal transition (EndoMT) mitochondrial function. After administration, we found M1-BMDMs significantly promoted EndoMT in vitro vivo, which aggravated BSCB SCI. In addition, significant dysfunction mitochondria reactive oxygen species (ROS) also detected. Furthermore, bioinformatics analysis demonstrated that miR-155 is upregulated both microglia. Experimentally, exosomal transfer participated M1-BMDMs-induced ROS generation cells, subsequently activated NF-κB signaling pathway targeting downstream suppressor cytokine 6 (SOCS6), suppressing SOCS6-mediated p65 ubiquitination degradation. Finally, series rescue assay further verified miR155/SOCS6/p65 axis regulated process function cells. summary, work revealed potential mechanism describing communications between could benefit for future research aid development therapies