4.7 Article

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

期刊

REDOX BIOLOGY
卷 41, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.redox.2021.101932

关键词

Spinal cord injury; Blood-spinal-cord-barrier; miR-155/SOCS6/p65; Endothelial-to-mesenchymal transition; Mitochondria

资金

  1. National Natural Science Foundation of China [81974335]
  2. Natural Science Foundation of Jiangsu Province [BK20181490]
  3. Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX20_0475]
  4. Six Talent Peaks Project in Jiangsu Province [TD-SWYY-010]
  5. Wu Jieping Medical Foundation

向作者/读者索取更多资源

The study revealed that M1-BMDMs promote EndoMT of vascular endothelial cells, exacerbating BSCB disruption after SCI and causing dysfunction of mitochondria and accumulation of ROS. Exosomal miR-155/SOCS6/p65 axis plays a crucial role in regulating EndoMT process and mitochondrial function in vascular endothelial cells.
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-.B 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.

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