Research Paper Volume 13, Issue 5 pp 7067—7083
GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris
- 1 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- 2 Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- 3 Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China
- 4 Department of Orthopedics, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian 223600, China
- 5 Department of Orthopedics, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, China
- 6 Department of Orthopedics, Xishan People's Hospital, Wuxi 214000, China
Received: October 5, 2020 Accepted: November 27, 2020 Published: February 17, 2021https://doi.org/10.18632/aging.202560
How to Cite
Copyright: © 2021 Wan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). As phagocytes do, microvascular endothelial cells (MECs) participate in myelin debris clearance at the injury site within one week. Our group has verified that G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) is essential in autophagy and angiogenesis, both of which are tightly related to the uptake and degradation of myelin debris by MECs. Here, we analyzed the performance and mechanism of GIT1 in myelin debris clearance after SCI. The SCI contusion model was established and in vitro MECs were treated with myelin debris. Better recovery from traumatic SCI was observed in the GIT1 WT mice than in the GIT1 KO mice. More importantly, we found that GIT1 prompted MECs to clear myelin debris and further enhanced MECs angiogenesis in vivo and in vitro. Mechanistically, GIT1-mediated autophagy contributed to the clearance of myelin debris by MECs. In this study, we demonstrated that GIT1 may prompt MECs to clear myelin debris via autophagy and further stimulate MECs angiogenesis via upregulating VEGF. Our results indicate that GITI may serve as a promising target for accelerating myelin debris clearance and improving SCI recovery.
SCI: spinal cord injury; GIT1: g protein-coupled receptor kinase 2 interacting protein-1; MEP: motor-evoked potential; GFAP: glial fibrillary acidic protein; MBP: myelin basic protein; WT: wild type; KO: knockout; BMECs: brain microvascular endothelial cells; CFSE: carboxyfluorescein succinimidyl ester; VEGF: vascular endothelial growth factor.