Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis

Exosomes are nano-sized vesicles that contain a variety of mRNAs, miRNAs, and proteins. They are capable of being released by a variety of cells and are essential for cell–cell communication. The exosomes produced by cells have shown protective benefits against spinal cord damage (SCI). Recently, it...

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Main Authors: Jiang-Hu Huang, Hang He, Yong-Neng Chen, Zhen Liu, Manini Daudi Romani, Zhao-Yi Xu, Yang Xu, Fei-Yue Lin
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/12/10/1322
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author Jiang-Hu Huang
Hang He
Yong-Neng Chen
Zhen Liu
Manini Daudi Romani
Zhao-Yi Xu
Yang Xu
Fei-Yue Lin
author_facet Jiang-Hu Huang
Hang He
Yong-Neng Chen
Zhen Liu
Manini Daudi Romani
Zhao-Yi Xu
Yang Xu
Fei-Yue Lin
author_sort Jiang-Hu Huang
collection DOAJ
description Exosomes are nano-sized vesicles that contain a variety of mRNAs, miRNAs, and proteins. They are capable of being released by a variety of cells and are essential for cell–cell communication. The exosomes produced by cells have shown protective benefits against spinal cord damage (SCI). Recently, it was discovered that M2 macrophages aid in the angiogenesis of numerous illnesses. However, the functional role of M2 macrophage-derived exosomes on SCI is unclear. Here, we investigate the pro-angiogenesis of M2 macrophage-derived exosomes on SCI. We founded that M2 macrophage exosomes alleviated tissue damage and enhanced functional recovery post-SCI. We discovered that M2 macrophage exosome administration increased angiogenesis after SCI in vivo using immunohistochemistry, immunofluorescence labeling, and Western blot analysis. Additionally, the expression of the pro-angiogenesis factors, HIF-1α and VEGF, were enhanced with the treatment of the M2 macrophage exosomes. Furthermore, we found that M2 macrophage exosomes enhanced neurogenesis after SCI in vivo. In vitro, we found that M2 macrophage exosomes can be taken up by the brain endothelial cell line (bEnd.3) and that they enhanced the tube formation, migration, and proliferation of bEnd.3 cells. Furthermore, by using special siRNA to inhibit HIF-1α expression, we observed that the expression of VEGF decreased, and the tube formation, migration, and proliferation of bEnd.3 cells were attenuated with the treatment of HIF-1α-siRNA. In conclusion, our findings reveal that M2 macrophage exosomes improve neurological functional recovery and angiogenesis post-SCI, and this process is partially associated with the activation of the HIF-1/VEGF signaling pathway.
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spelling doaj.art-cfec468fc81d4552bd60e35d6b7fc9082023-11-23T23:13:33ZengMDPI AGBrain Sciences2076-34252022-09-011210132210.3390/brainsci12101322Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF AxisJiang-Hu Huang0Hang He1Yong-Neng Chen2Zhen Liu3Manini Daudi Romani4Zhao-Yi Xu5Yang Xu6Fei-Yue Lin7Department of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Social Economy and Business Administration, Woosuk University, Wanju-gun 55338, KoreaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, ChinaExosomes are nano-sized vesicles that contain a variety of mRNAs, miRNAs, and proteins. They are capable of being released by a variety of cells and are essential for cell–cell communication. The exosomes produced by cells have shown protective benefits against spinal cord damage (SCI). Recently, it was discovered that M2 macrophages aid in the angiogenesis of numerous illnesses. However, the functional role of M2 macrophage-derived exosomes on SCI is unclear. Here, we investigate the pro-angiogenesis of M2 macrophage-derived exosomes on SCI. We founded that M2 macrophage exosomes alleviated tissue damage and enhanced functional recovery post-SCI. We discovered that M2 macrophage exosome administration increased angiogenesis after SCI in vivo using immunohistochemistry, immunofluorescence labeling, and Western blot analysis. Additionally, the expression of the pro-angiogenesis factors, HIF-1α and VEGF, were enhanced with the treatment of the M2 macrophage exosomes. Furthermore, we found that M2 macrophage exosomes enhanced neurogenesis after SCI in vivo. In vitro, we found that M2 macrophage exosomes can be taken up by the brain endothelial cell line (bEnd.3) and that they enhanced the tube formation, migration, and proliferation of bEnd.3 cells. Furthermore, by using special siRNA to inhibit HIF-1α expression, we observed that the expression of VEGF decreased, and the tube formation, migration, and proliferation of bEnd.3 cells were attenuated with the treatment of HIF-1α-siRNA. In conclusion, our findings reveal that M2 macrophage exosomes improve neurological functional recovery and angiogenesis post-SCI, and this process is partially associated with the activation of the HIF-1/VEGF signaling pathway.https://www.mdpi.com/2076-3425/12/10/1322M2 macrophage-derived exosomesangiogenesisHIF-1αspinal cord injuryfunctional recovery
spellingShingle Jiang-Hu Huang
Hang He
Yong-Neng Chen
Zhen Liu
Manini Daudi Romani
Zhao-Yi Xu
Yang Xu
Fei-Yue Lin
Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis
Brain Sciences
M2 macrophage-derived exosomes
angiogenesis
HIF-1α
spinal cord injury
functional recovery
title Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis
title_full Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis
title_fullStr Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis
title_full_unstemmed Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis
title_short Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis
title_sort exosomes derived from m2 macrophages improve angiogenesis and functional recovery after spinal cord injury through hif 1α vegf axis
topic M2 macrophage-derived exosomes
angiogenesis
HIF-1α
spinal cord injury
functional recovery
url https://www.mdpi.com/2076-3425/12/10/1322
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