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VEGFR2 signaling drives meningeal vascular regeneration upon head injury

Author

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  • Bong Ihn Koh

    (KI for Bio-century, Korea Advanced Institute of Science and Technology (KAIST))

  • Hyuek Jong Lee

    (Center for Vascular Research, Institute for Basic Science (IBS))

  • Pil Ae Kwak

    (Center for Vascular Research, Institute for Basic Science (IBS))

  • Myung Jin Yang

    (Center for Vascular Research, Institute for Basic Science (IBS)
    Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)

  • Ju-Hee Kim

    (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)

  • Hyung-Seok Kim

    (Chonnam National University Medical School)

  • Gou Young Koh

    (KI for Bio-century, Korea Advanced Institute of Science and Technology (KAIST)
    Center for Vascular Research, Institute for Basic Science (IBS)
    Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)

  • Injune Kim

    (KI for Bio-century, Korea Advanced Institute of Science and Technology (KAIST)
    Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)

Abstract

Upon severe head injury (HI), blood vessels of the meninges and brain parenchyma are inevitably damaged. While limited vascular regeneration of the injured brain has been studied extensively, our understanding of meningeal vascular regeneration following head injury is quite limited. Here, we identify key pathways governing meningeal vascular regeneration following HI. Rapid and complete vascular regeneration in the meninges is predominantly driven by VEGFR2 signaling. Substantial increase of VEGFR2 is observed in both human patients and mouse models of HI, and endothelial cell-specific deletion of Vegfr2 in the latter inhibits meningeal vascular regeneration. We further identify the facilitating, stabilizing and arresting roles of Tie2, PDGFRβ and Dll4 signaling, respectively, in meningeal vascular regeneration. Prolonged inhibition of this angiogenic process following HI compromises immunological and stromal integrity of the injured meninges. These findings establish a molecular framework for meningeal vascular regeneration after HI, and may guide development of wound healing therapeutics.

Suggested Citation

  • Bong Ihn Koh & Hyuek Jong Lee & Pil Ae Kwak & Myung Jin Yang & Ju-Hee Kim & Hyung-Seok Kim & Gou Young Koh & Injune Kim, 2020. "VEGFR2 signaling drives meningeal vascular regeneration upon head injury," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17545-2
    DOI: 10.1038/s41467-020-17545-2
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