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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

Authors :
Feng Wang
Xinglin Chen
Guoyong Yin
Xiaoyan Li
Chen Xichen
Weihua Cai
Wang Zibin
Yang Liu
Jin Fan
Wei Liu
Xuhui Ge
Wene Zhao
Xiao Lu
Zhiyang Xu
Yuluo Rong
Chengyue Ji
Pengyu Tang
Ao Duan
Chenyu Huang
Jiaxing Wang
Dongdong Jiang
Source :
Redox Biology, Vol 41, Iss, Pp 101932-(2021), Redox Biology
Publication Year :
2021
Publisher :
Elsevier, 2021.

Abstract

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 macrophages are dominant and play a crucial role throughout the whole SCI process. The aim of our study was to investigate the effects of M1-polarized bone marrow-derived macrophages (M1-BMDMs) on vascular endothelial cells and their underlying mechanism. Microvascular endothelial cell line bEnd.3 cells were treated with conditioned medium or exosomes derived from M1-BMDMs, followed by evaluations of endothelial-to-mesenchymal transition (EndoMT) and mitochondrial function. After administration, we found conditioned medium or exosomes from M1-BMDMs significantly promoted EndoMT of vascular endothelial cells in vitro and in vivo, which aggravated BSCB disruption after SCI. In addition, significant dysfunction of mitochondria and accumulation of reactive oxygen species (ROS) were also detected. Furthermore, bioinformatics analysis demonstrated that miR-155 is upregulated in both M1-polarized macrophages and microglia. Experimentally, exosomal transfer of miR-155 participated in M1-BMDMs-induced EndoMT and mitochondrial ROS generation in bEnd.3 cells, and subsequently activated the NF-κB signaling pathway by targeting downstream suppressor of cytokine signaling 6 (SOCS6), and suppressing SOCS6-mediated p65 ubiquitination and degradation. Finally, a series of rescue assay further verified that exosomal miR155/SOCS6/p65 axis regulated the EndoMT process and mitochondrial function in vascular endothelial cells. In summary, our work revealed a potential mechanism describing the communications between macrophages and vascular endothelial cells after SCI which could benefit for future research and aid in the development of potential therapies for SCI.<br />Graphical abstract Image 1<br />Highlights • BSCB is disrupted after SCI leading to infiltration of macrophages. • Exosomes from M1-polarized-macrophages promote EndoMT and impair mitochondrial function in vascular endothelial cells. • miR-155 is upregulated in exosomes derived from M1-polarized macrophages. • Exosomal miR-155/SOCS6/p65 axis is involved in EndoMT and mitochondrial dysfunction of vascular endothelial cells.

Details

Language :
English
ISSN :
22132317
Volume :
41
Database :
OpenAIRE
Journal :
Redox Biology
Accession number :
edsair.doi.dedup.....32f8d54414ed28bb378105c0ff640faa