Perlecan regulates pericyte dynamics in the maintenance and repair of the blood–brain barrier

DOI PDF 被引用文献6件 参考文献59件
  • Kuniyuki Nakamura
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1
  • Tomoko Ikeuchi
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1
  • Kazuki Nara
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1
  • Craig S. Rhodes
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1
  • Peipei Zhang
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1
  • Yuta Chiba
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1
  • Saiko Kazuno
    Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan 4
  • Yoshiki Miura
    Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan 4
  • Tetsuro Ago
    Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 2
  • Eri Arikawa-Hirasawa
    Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan 5
  • Yoh-suke Mukouyama
    Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 6
  • Yoshihiko Yamada
    Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1

説明

<jats:p>Ischemic stroke causes blood–brain barrier (BBB) breakdown due to significant damage to the integrity of BBB components. Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFRβ up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan of basement membranes, aids in BBB maintenance and repair through pericyte interactions. Using a transient middle cerebral artery occlusion model, we found larger infarct volumes and more BBB leakage in conditional perlecan (Hspg2)-deficient (Hspg2−/−-TG) mice than in control mice. Control mice showed increased numbers of pericytes in the ischemic lesion, whereas Hspg2−/−-TG mice did not. At the mechanistic level, pericytes attached to recombinant perlecan C-terminal domain V (perlecan DV, endorepellin). Perlecan DV enhanced the PDGF-BB–induced phosphorylation of PDGFRβ, SHP-2, and FAK partially through integrin α5β1 and promoted pericyte migration. Perlecan therefore appears to regulate pericyte recruitment through the cooperative functioning of PDGFRβ and integrin α5β1 to support BBB maintenance and repair following ischemic stroke.</jats:p>

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