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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
- 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.
- Subjects :
- 0301 basic medicine
Mitochondrial ROS
Medicine (General)
QH301-705.5
Clinical Biochemistry
Endothelial-to-mesenchymal transition
Spinal cord injury
Blood-spinal-cord-barrier
Mitochondrion
Biochemistry
miR-155
03 medical and health sciences
0302 clinical medicine
R5-920
Downregulation and upregulation
medicine
SOCS6
Biology (General)
miR-155/SOCS6/p65
Microglia
Chemistry
Organic Chemistry
Microvesicles
Cell biology
Mitochondria
Endothelial stem cell
030104 developmental biology
medicine.anatomical_structure
030217 neurology & neurosurgery
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....32f8d54414ed28bb378105c0ff640faa