Endothelial Barrier Strengthening by Activation of Focal Adhesion Kinase

Endothelial cell barrier (EC) properties regulate blood tissue fluid flux. To determine the role of endothelial-matrix interactions in barrier regulation, we induced cell shrinkage by exposing confluent endothelial monolayers to hyperosmolarity. The dominant effect of a 15-min hyperosmolar exposure...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-04, Vol.278 (15), p.13342-13349
Main Authors: Quadri, Sadiqa K, Bhattacharjee, Mrinal, Parthasarathi, Kaushik, Tanita, Tatsuo, Bhattacharya, Jahar
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Endothelium, Vascular - physiology
Enzyme Activation
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Kinetics
Lung
Microcirculation
Osmolar Concentration
Plasmids
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Pulmonary Circulation
Rats
Recombinant Proteins - metabolism
Transfection
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Summary:Endothelial cell barrier (EC) properties regulate blood tissue fluid flux. To determine the role of endothelial-matrix interactions in barrier regulation, we induced cell shrinkage by exposing confluent endothelial monolayers to hyperosmolarity. The dominant effect of a 15-min hyperosmolar exposure was an increase in the trans-endothelial electrical resistance, indicating the induction of barrier strengthening. Hyperosmolar exposure also increased activity of focal adhesion kinase and E-cadherin accumulation at the cell periphery. Concomitantly, the density of actin filaments increased markedly. In EC monolayers stably expressing constitutively active or dominant negative isoforms of Rac1, the actin response to hyperosmolar exposure was enhanced or blocked, respectively, although the response in trans-endothelial resistance was unaffected, indicating that the endothelial barrier enhancement occurred independently of actin. However, in monolayers expressing a kinase-deficient mutant of focal adhesion kinase, the hyperosmolarity-induced increases in activity of focal adhesion and peripheral E-cadherin enhancement were blocked and the induced increase of electrical resistance was markedly blunted. These findings indicate that in EC exposed to hyperosmolar challenge, the involvement of focal adhesion kinase was critical in establishing barrier strengthening.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M209922200