Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4

Jing Qiao, Fei Huang, Ram P. Naikawadi, Kwang Sik Kim, Tamer Said, Hazel Lum

Research output: Contribution to journalArticle

Abstract

Abundant evidence indicates that lysophosphatidylcholine (LPC) is proinflammatory and atherogenic. In the vascular endothelium, LPC increases permeability and expression of proinflammatory molecules such as adhesion molecules and cytokines. Yet, mechanisms by which LPC mediates these activities remain unclear and controversial. Recent evidence implicates involvement of a novel subfamily of G protein-coupled receptors (GPR4, G2A, OGR1, and TDAG8) that are sensitive to lysolipids and protons. We previously reported that one of these receptors, GPR4, is selectively expressed by a variety of endothelial cells and therefore hypothesize that the LPC-stimulated endothelial barrier dysfunction is mediated through GPR4. We developed a peptide Ab against GPR4 that detected GPR4 expression in transfected COS 7 cells and endogenous GPR4 expression in endothelial cells by Western blot. Endothelial cells infected with a retrovirus containing small interference RNA (siRNA) to GPR4 resulted in 40-50% decreased GPR4 expression, which corresponded with partial prevention of the LPC-induced 1) decrease in transendothelial resistance, 2) stress fiber formation, and 3) activation of RhoA. Furthermore, coexpression of the siRNA-GPR4 with a siRNA-resistant mutant GPR4 fully restored the LPC-induced resistance decrease. However, extracellular pH of

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number1
DOIs
StatePublished - 2006

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Lysophosphatidylcholines
G-Protein-Coupled Receptors
RNA Interference
Endothelial Cells
Stress Fibers
COS Cells
Vascular Endothelium
Retroviridae
Protons
Permeability
Western Blotting
Cytokines
Peptides

Keywords

  • Actin
  • Endothelial resistance
  • RhoA
  • Small interference ribonucleic acid

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4. / Qiao, Jing; Huang, Fei; Naikawadi, Ram P.; Kim, Kwang Sik; Said, Tamer; Lum, Hazel.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 1, 2006.

Research output: Contribution to journalArticle

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AU - Lum, Hazel

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