Vascular Endothelial Growth Factor Enhances Axonal Outgrowth in Organotypic Spinal Cord Slices via Vascular Endothelial Growth Factor Receptor 1 and 2.
10.1007/s13770-016-0051-9
- Author:
Hwan Woo PARK
1
;
Hyo Jin JEON
;
Mi Sook CHANG
Author Information
1. Laboratory of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute & School of Dentistry, Seoul National University, Seoul, Korea. mschang@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Vascular endothelial growth factor;
Neurotrophic factor;
Spinal cord;
Organotypic culture;
Receptors
- MeSH:
Adult;
Axons*;
Humans;
Inflammation;
Nerve Regeneration;
Neurites;
Neuroglia;
Neurons;
Protein Kinases;
Receptors, Vascular Endothelial Growth Factor*;
Spinal Cord Injuries;
Spinal Cord*;
Spinal Nerves;
Vascular Endothelial Growth Factor A*;
Vascular Endothelial Growth Factor Receptor-1*
- From:
Tissue Engineering and Regenerative Medicine
2016;13(5):601-609
- CountryRepublic of Korea
- Language:English
-
Abstract:
Enhancing adult nerve regeneration is a potential therapeutic strategy for treating spinal cord injury. Vascular endothelial growth factor (VEGF) is a major contributor to angiogenesis, which can reduce the spinal cord injury by inhibiting the inflammation and improve recovery after spinal cord injury. We have previously demonstrated that exogenous VEGF has neurotrophic effects on injured spinal nerves in organotypic spinal cord slice cultures. However, the mechanisms underlying the neurite growth by exogenous VEGF remain to be explored in spinal cord. In this study, we found out that exogenous VEGF mediated axonal outgrowth through VEGF receptor 1 (VEGFR1) and VEGFR2, both of which were expressed on organotypic spinal cord slices. Although VEGFR1 and VEGFR2 were constitutively expressed in some cells of control spinal cord slices, VEGF treatment upregulated expression of VEGFR1 and VEGFR2. Both VEGFR1 and VEGFR2 were expressed in neuronal cells as well as glial cells of organotypic spinal cord slices. We also observed that VEGF-induced axonal outgrowth was attenuated by a specific mitogen-activated protein kinase (MAPK) inhibitor PD98059 and a specific phosphoinositide 3-kinase (PI3K) inhibitor wortmannin. Thus, these findings suggest that these MAPK and PI3K pathways have important roles in regulating VEGF-induced axonal outgrowth in the postnatal spinal cord.
