Open AccessVascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury
Author(s) -
Liu SuMei,
Xiao ZhiFeng,
Li Xing,
Zhao YanNan,
Wu XianMing,
Han Jin,
Chen Bing,
Li JiaYin,
Fan CaiXia,
Xu Bai,
Xue XiaoYu,
Xue WeiWei,
Yang Ying,
Dai JianWu
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13056
Subject(s) - neural stem cell , spinal cord , vascular endothelial growth factor , spinal cord injury , epidermal growth factor receptor , kinase insert domain receptor , medicine , cancer research , microbiology and biotechnology , vascular endothelial growth factor a , neuroscience , receptor , biology , vegf receptors , stem cell
Summary 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.