[논문]VEGFR2 signaling drives meningeal vascular regeneration upon head injury

Koh, Bong Ihn; Lee, Hyuek Jong; Kwak, Pil Ae; Yang, Myung Jin; Kim, Ju-Hee; Kim, Hyung-Seok; Koh, Gou Young; Kim, Injune

doi:10.1038/s41467-020-17545-2

[해외논문] VEGFR2 signaling drives meningeal vascular regeneration upon head injury 원문보기

Nature communications, v.11 no.1 = v.11, 2020년, pp.3866 -

Koh, Bong Ihn (KI for Bio-century, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141 Republic of Korea) , Lee, Hyuek Jong (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Kwak, Pil Ae (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Yang, Myung Jin (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Kim, Ju-Hee (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141 Republic of Korea) , Kim, Hyung-Seok (Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, 61463 Republic of Korea) , Koh, Gou Young (KI for Bio-century, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141 Republic of Korea) , Kim, Injune (KI for Bio-century, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141 Republic of Korea)

Abstract ▼ AI-Helper

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.Severe head injury results in critical damage of blood vessels of the meninges and brain parenchyma. Here, the authors describe key pathways governing meningeal vascular regeneration following head injury, characterizing the differential roles of VEGFR2, Tie2, Dll4 and PDGFRβ signaling.

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