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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 291 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4
AU - Qiao, Jing
AU - Huang, Fei
AU - Naikawadi, Ram P.
AU - Kim, Kwang Sik
AU - Said, Tamer
AU - Lum, Hazel
PY - 2006
Y1 - 2006
N2 - 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
AB - 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
KW - Actin
KW - Endothelial resistance
KW - RhoA
KW - Small interference ribonucleic acid
UR - http://www.scopus.com/inward/record.url?scp=33745686063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745686063&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00508.2005
DO - 10.1152/ajplung.00508.2005
M3 - Article
C2 - 16461426
AN - SCOPUS:33745686063
VL - 291
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 1
ER -