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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MDPI AG
2022-09-01
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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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