Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation

Shui Q. Ye, Li Q. Zhang, Djanybek Adyshev, Peter V. Usatyuk, Alexander N. Garcia, Tera L. Lavoie, Alexander D. Verin, Viswanathan Natarajan, Joe G.N. Garcia

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Prior genomic and genetic studies identified pre-B-cell colony-enhancing factor (PBEF) as a novel candidate gene and biomarker in acute lung injury (ALI). As increased vascular permeability is a cardinal feature of ALI, we assessed the role of PBEF in in vitro vascular barrier regulation using confluent human pulmonary artery endothelial cell (HPAEC) monolayers. Reductions in PBEF protein expression (>70%) by siRNA significantly attenuated EC barrier dysfunction induced by the potent edemagenic agent, thrombin, reflected by reductions in transendothelial electric resistance (TER, ∼60% reduction). Furthermore, PBEF siRNA blunted thrombin-mediated increases in Ca2+ entry, polymerized actin formation, and myosin light chain phosphorylation, events critical to the thrombin-mediated permeability response. Finally, PBEF siRNA also significantly inhibited thrombin-stimulated increase of IL-8 secretion in HPAEC, a chemokine known to induce actin fiber formation and intercellular gap formation of endothelial cells. Taken together, these studies demonstrate that PBEF may be required for complete expression of the thrombin-induced inflammatory response and reveal potentially novel role for PBEF in the regulation of EC Ca2+-dependent cytoskeletal rearrangement and endothelial barrier dysfunction. Ongoing studies will continue to address the molecular mechanisms by which PBEF contributes to ALI susceptibility.

Original languageEnglish (US)
Pages (from-to)142-151
Number of pages10
JournalMicrovascular Research
Volume70
Issue number3
DOIs
Publication statusPublished - Nov 1 2005
Externally publishedYes

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Keywords

  • Acute lung injury
  • Cytoskeleton
  • Pulmonary permeability
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Ye, S. Q., Zhang, L. Q., Adyshev, D., Usatyuk, P. V., Garcia, A. N., Lavoie, T. L., ... Garcia, J. G. N. (2005). Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvascular Research, 70(3), 142-151. https://doi.org/10.1016/j.mvr.2005.08.003