Endothelial barrier strengthening by activation of focal adhesion kinase

Sadiqa K. Quadri, Mrinal Bhattacharjee, Kaushik Parthasarathi, Tatsuo Tanita, Jahar Bhattacharya

Research output: Contribution to journalArticle

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Abstract

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 transendothelial 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.

Original languageEnglish (US)
Pages (from-to)13342-13349
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number15
DOIs
StatePublished - Apr 11 2003

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Focal Adhesion Protein-Tyrosine Kinases
Endothelial cells
Actins
Monolayers
Acoustic impedance
Endothelial Cells
Chemical activation
Cadherins
Electric Impedance
Focal Adhesions
Actin Cytoskeleton
Protein Isoforms
Blood
Phosphotransferases
Adhesion
Tissue
Fluxes
Fluids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Endothelial barrier strengthening by activation of focal adhesion kinase. / Quadri, Sadiqa K.; Bhattacharjee, Mrinal; Parthasarathi, Kaushik; Tanita, Tatsuo; Bhattacharya, Jahar.

In: Journal of Biological Chemistry, Vol. 278, No. 15, 11.04.2003, p. 13342-13349.

Research output: Contribution to journalArticle

Quadri, Sadiqa K. ; Bhattacharjee, Mrinal ; Parthasarathi, Kaushik ; Tanita, Tatsuo ; Bhattacharya, Jahar. / Endothelial barrier strengthening by activation of focal adhesion kinase. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 15. pp. 13342-13349.
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