Fc-saxatilin inhibits VEGF-induced permeability by regulating claudin-5 expression in human brain microvascular endothelial cells

Hyun Jung Choi, Na Eun Kim, Il Kwon, Dukhwan Choi, Jayoung Kim, Ji Hoe Heo

Research output: Contribution to journalArticle

Abstract

The disruption of the blood–brain barrier influences the degree of brain damage and prognosis in cerebral ischemia or other brain diseases accompanied by inflammation. Vascular endothelial growth factor (VEGF) released during brain ischemia or inflammation has been implicated in the breakdown of the blood–brain barrier by increasing endothelial permeability. Saxatilin, a disintegrin-containing RGD motif, has been reported to disaggregate platelets via interactions with platelet integrins and to have a thrombolysis effect. Additionally, the Fc–saxatilin fusion protein reduces vascular leakage in cerebral ischemia in mice. In this study, we show that Fc–saxatilin prevents VEGF-induced permeability in human brain microvascular endothelial cells (HBMECs). The activation of Src and Fak, downstream signaling proteins of VEGF in the induction of endothelial permeability, was inhibited by Fc–saxatilin in HBMECs. The downregulation of a tight junction protein, claudin-5, at the protein and mRNA levels by VEGF was recovered by Fc–saxatilin. Our findings suggest that Fc–saxatilin attenuates VEGF-induced endothelial permeability via the regulation of downstream signaling, and this may contribute to its protective effect against vascular leakage in the ischemic brain.

Original languageEnglish
Article number103953
JournalMicrovascular Research
Volume128
DOIs
Publication statusPublished - 2020 Mar

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Claudin-5
Endothelial cells
Vascular Endothelial Growth Factor A
Permeability
Brain
Endothelial Cells
Brain Ischemia
Blood Vessels
Platelets
Blood Platelets
Tight Junction Proteins
Disintegrins
Proteins
Brain Diseases
Encephalitis
Integrins
Down-Regulation
saxatilin
Inflammation
Fusion reactions

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

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abstract = "The disruption of the blood–brain barrier influences the degree of brain damage and prognosis in cerebral ischemia or other brain diseases accompanied by inflammation. Vascular endothelial growth factor (VEGF) released during brain ischemia or inflammation has been implicated in the breakdown of the blood–brain barrier by increasing endothelial permeability. Saxatilin, a disintegrin-containing RGD motif, has been reported to disaggregate platelets via interactions with platelet integrins and to have a thrombolysis effect. Additionally, the Fc–saxatilin fusion protein reduces vascular leakage in cerebral ischemia in mice. In this study, we show that Fc–saxatilin prevents VEGF-induced permeability in human brain microvascular endothelial cells (HBMECs). The activation of Src and Fak, downstream signaling proteins of VEGF in the induction of endothelial permeability, was inhibited by Fc–saxatilin in HBMECs. The downregulation of a tight junction protein, claudin-5, at the protein and mRNA levels by VEGF was recovered by Fc–saxatilin. Our findings suggest that Fc–saxatilin attenuates VEGF-induced endothelial permeability via the regulation of downstream signaling, and this may contribute to its protective effect against vascular leakage in the ischemic brain.",
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Fc-saxatilin inhibits VEGF-induced permeability by regulating claudin-5 expression in human brain microvascular endothelial cells. / Choi, Hyun Jung; Kim, Na Eun; Kwon, Il; Choi, Dukhwan; Kim, Jayoung; Heo, Ji Hoe.

In: Microvascular Research, Vol. 128, 103953, 03.2020.

Research output: Contribution to journalArticle

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AU - Kim, Jayoung

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