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β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability.

Publication ,  Journal Article
Izawa, Y; Gu, Y-H; Osada, T; Kanazawa, M; Hawkins, BT; Koziol, JA; Papayannopoulou, T; Spatz, M; Del Zoppo, GJ
Published in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
April 2018

Acutely following focal cerebral ischemia disruption of the microvessel blood-brain barrier allows transit of plasma proteins into the neuropil as edema formation that coincides with loss of microvessel endothelial β1-integrins. We extend previous findings to show that interference with endothelial β1-integrin-matrix adhesion by the monoclonal IgM Ha2/5 increases the permeability of primary cerebral microvascular endothelial cell monolayers through reorganization of claudin-5, occludin, and zonula occludens-1 (ZO-1) from inter-endothelial borders. Interference with β1-integrin-matrix adhesion initiates F-actin conformational changes that coincide with claudin-5 redistribution. β1-integrin-matrix interference simultaneously increases phosphorylation of myosin light chain (MLC), while inhibition of MLC kinase (MLCK) and Rho kinase (ROCK) abolishes the Ha2/5-dependent increased endothelial permeability by 6 h after β1-integrin-matrix interference. These observations are supported by concordant observations in the cortex of a high-quality murine conditional β1-integrin deletion construct. Together they support the hypothesis that detachment of β1-integrins from abluminal matrix ligands increases vascular endothelial permeability through reorganization of tight junction (TJ) proteins via altered F-actin conformation, and indicate that the β1-integrin-MLC signaling pathway is engaged when β1-integrin detachment occurs. These findings provide a novel approach to the research and treatment of cerebral disorders where the breakdown of the blood-brain barrier accounts for their progression and complication.

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Published In

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

DOI

EISSN

1559-7016

ISSN

0271-678X

Publication Date

April 2018

Volume

38

Issue

4

Start / End Page

641 / 658

Related Subject Headings

  • Tight Junctions
  • Tight Junction Proteins
  • Protein Conformation
  • Neurology & Neurosurgery
  • Myosin Light Chains
  • Microvessels
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Integrin beta1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Izawa, Y., Gu, Y.-H., Osada, T., Kanazawa, M., Hawkins, B. T., Koziol, J. A., … Del Zoppo, G. J. (2018). β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 38(4), 641–658. https://doi.org/10.1177/0271678x17722108
Izawa, Yoshikane, Yu-Huan Gu, Takashi Osada, Masato Kanazawa, Brian T. Hawkins, James A. Koziol, Thalia Papayannopoulou, Maria Spatz, and Gregory J. Del Zoppo. “β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability.Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism 38, no. 4 (April 2018): 641–58. https://doi.org/10.1177/0271678x17722108.
Izawa Y, Gu Y-H, Osada T, Kanazawa M, Hawkins BT, Koziol JA, et al. β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2018 Apr;38(4):641–58.
Izawa, Yoshikane, et al. “β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability.Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 38, no. 4, Apr. 2018, pp. 641–58. Epmc, doi:10.1177/0271678x17722108.
Izawa Y, Gu Y-H, Osada T, Kanazawa M, Hawkins BT, Koziol JA, Papayannopoulou T, Spatz M, Del Zoppo GJ. β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2018 Apr;38(4):641–658.
Journal cover image

Published In

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

DOI

EISSN

1559-7016

ISSN

0271-678X

Publication Date

April 2018

Volume

38

Issue

4

Start / End Page

641 / 658

Related Subject Headings

  • Tight Junctions
  • Tight Junction Proteins
  • Protein Conformation
  • Neurology & Neurosurgery
  • Myosin Light Chains
  • Microvessels
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Integrin beta1