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Vascular endothelial growth factor enhances axonal outgrowth in organotypic spinal cord slices via vascular endothelial growth factor receptor 1 and 2

  • Original Article
  • Regenerative Medicine
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

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.

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Authors and Affiliations

  1. Laboratory of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute & School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

    Hwan-Woo Park, Hyo-Jin Jeon & Mi-Sook Chang

  2. Department of Cell Biology, College of Medicine, Konyang University, Daejeon, Korea

    Hwan-Woo Park

  3. Neuroscience Research Institute, Seoul National University, Seoul, Korea

    Mi-Sook Chang

Authors
  1. Hwan-Woo Park
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  2. Hyo-Jin Jeon
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  3. Mi-Sook Chang
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Correspondence to Mi-Sook Chang.

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Park, HW., Jeon, HJ. & Chang, MS. Vascular endothelial growth factor enhances axonal outgrowth in organotypic spinal cord slices via vascular endothelial growth factor receptor 1 and 2. Tissue Eng Regen Med 13, 601–609 (2016). https://doi.org/10.1007/s13770-016-0051-9

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  • DOI: https://doi.org/10.1007/s13770-016-0051-9

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