Vascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury.
AIMS
Neural stem cells (NSCs) in the adult mammalian spinal cord are activated in response to spinal cord injury (SCI); however, mechanisms modulating this process are not clear. Here, we noticed SCI elevated expression of vascular endothelial growth factor (VEGF) and we aimed to validate the roles of VEGF in NSCs activation after SCI and investigated the related signals during the process.


METHODS
In vitro we detected whether VEGF promoted spinal cord NSCs proliferation and investigated the involved signals; In vivo, we injected VEGF into rat spinal cord to check the NSCs activation.


RESULTS
In vitro, VEGF triggered spinal cord NSCs proliferation and maintained self-renewal. Further investigations demonstrated VEGF transactivated epidermal growth factor receptor (EGFR) through VEGF receptor 2 (VEGFR2) to promote spinal cord NSCs proliferation. In vivo, we injected VEGF into spinal cord by laminectomy to confirm the roles of VEGF-VEGFR2-EGFR signals in NSCs activation. VEGF significantly elevated the number of activated NSCs and increased EGFR phosphorylation. In contrast, intraspinal injection of specific inhibitors targeting EGFR and VEGFR2 decreased NSCs activation after SCI. Our results demonstrate that VEGF-VEGFR2-EGFR axis is important for NSCs activation after SCI, providing new insights into the mechanisms of spinal cord NSCs activation postinjury.
['Liu|Su-Mei|SM|', 'Xiao|Zhi-Feng|ZF|', 'Li|Xing|X|', 'Zhao|Yan-Nan|YN|', 'Wu|Xian-Ming|XM|', 'Han|Jin|J|', 'Chen|Bing|B|', 'Li|Jia-Yin|JY|', 'Fan|Cai-Xia|CX|', 'Xu|Bai|B|', 'Xue|Xiao-Yu|XY|', 'Xue|Wei-Wei|WW|', 'Yang|Ying|Y|', 'Dai|Jian-Wu|JW|0000-0002-3379-9053']
D000818:Animals D049109:Cell Proliferation D002478:Cells, Cultured D004195:Disease Models, Animal D066246:ErbB Receptors D005260:Female D058953:Neural Stem Cells D017207:Rats, Sprague-Dawley D015398:Signal Transduction D013116:Spinal Cord D013119:Spinal Cord Injuries D042461:Vascular Endothelial Growth Factor A D040301:Vascular Endothelial Growth Factor Receptor-2
vascular endothelial growth factor epidermal growth factor receptor spinal cord injury VEGF receptor 2 neural stem cells activation