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findings suggest an LPA1 receptor-dependent pathway by which LPA increases arteriolar release of mitochondria-derived hydrogen peroxide as a mediator of flow-induced dilation
his study uncovers an LPA1-EGFR signaling axis that is used for cell invasion in hypoxia and suggests a potential target to impede cancer metastasis
mRNA expression analyses revealed that ADSCs and MES largely expressed LPA receptor 1 (LPAR1) while epithelial cells mainly expressed LPAR6. LPA 18:1 activated all the cell populations and cell lines by rise in cytosolic free calcium concentrations. MES and ADSCs expressed ATX whereas epithelial cells did not.
In the presence of LPC, the cell motile activity of PANC-R9 cells was markedly stimulated. In contrast, LPC did not affect the cell motile activity of PANC-1 cells. PANC-R9 cell motility was inhibited by an ATX inhibitor, PF-8380. These results suggest that LPA signaling via LPA1 is a potent molecular target for the regulation of tumor progression in PANC-1 cells.
These results suggest a common molecular mechanism between myeloid differentiation of leukemia cells and migration of breast cancer cells depending on NM23 and EDG2 expression levels.
ATX-LPA axis facilitates estrogen-induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway.
DLD-C-F cells formed large-sized colonies, but not DLD-F-C cells, correlating with LPAR1 and LPAR6 gene expression levels. These results suggest that LPA1 and LPA6 may regulate the colony formation activity in DLD1 cells treated with anticancer drugs.
endogenous LPA1 receptor signaling and regulation
The increased expression of LPA and LPAR1 is associated with the fibrosis and hypertrophy of the ligamentum flavum in patients with Lumbar Spinal Stenosis.
myeloma cells stimulate mesenchymal stem cells (MSCs to produce autotaxin, an indispensable enzyme for the biosynthesis of lysophosphatidic acid, and LPA receptor 1 (LPA1) and 3 (LPA3) transduce opposite signals to MSCs to determine the fate of MSCs.
LPA1 plays a critical role in EGF responses and that FFA4 agonists inhibit proliferation by suppressing positive cross-talk between LPA1 and the EGF receptor
ADAMTS7 and LPA single nucleotide polymorphisms are related to a 24-h ambulatory systolic-diastolic pressure regression index.
Polymorphism rs7023923 located near LPAR1 gene: the association of rs7023923 with monocytosis was confirmed among healthy blood donors (p = 0.0156) but not among patients admitted for elective coronarography (p = 0.61).
These results suggest that autotaxin-LPA-LPA receptor 1-AKT1 signaling axis is critical for maintaining Cancer stem cells(CSC) characteristics through an autocrine loop and provide a novel therapeutic target for ovarian CSCs
LPA-type agonist, via Carbonyl-oxygen/Lys39 interaction facilitates the formation of a hypothetical N-terminal cap tightly packed over the LPA1 heptahelical bundle.
Data show high expression levels of LPAR2 and LPAR1 in endometrial cancer tissue with positive correlations with FIGO stage suggesting them as potential biomarkers for endometrial cancer progression.
Data suggest LPA (lysophosphatidic acid; acting via LPAR1) and endothelin activate Cdc42, concurrent with biphasic decrease in Rac1 activity, differential effects on RhoA; LPA/endothelin stim. leads to remodeling of invadosomes in melanoma cells.
we show that LPAR1 is a novel susceptibility gene for human essential hypertension and that stress, such as shortage of sleep, increases the susceptibility of patients with risk allele to essential hypertension.
Study presents three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses.
Results indicate that lysophosphatidic acid-lysophosphatidic acid receptor 1 (LPA-LPA1) signaling contributes to the activation of rheumatoid arthritis fibroblast-like synoviocytes (FLSs).
HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells.
Study shows that lysophosphatidic acid (LPA) propagates post-injury schwann cell (SC) dedifferentiation through lysophosphatidic acid 1 signaling. These data indicate that LPA may be a critical factor that shifts SCs towards a post-injury phenotype and contributes to the onset of Wallerian degeneration.
we demonstrate that LPA1/3 antagonism mildly reduced plasma LDL cholesterol levels. Therefore, pharmacological inhibition of LPA1/3 receptors may prove a promising approach to diminish atherosclerosis development.
LPA receptor 1 signaling increased TGFbeta expression via GSK3beta phosphorylation and SREBP1 activation, contributing to the development of diabetic nephropathy.
Our data suggest that LPAR signaling stimulates SS development by induction of IL-17 production via ROCK and p38 MAPK pathways. Thus, LPAR inhibition could be a possible therapeutic strategy for SS.
LPA-LPA1 signaling initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor.
Data (including data from studies conducted in cells from knockout mice) suggest that signaling via Lpar1, Cd14, and Scara1 mediates uptake of oxidized LDL by macrophages leading to foam cell formation; lysophosphatidic acid (LPA) induces expression of Cd14 and Scara1 in macrophages. (Lpar1 = LPA receptor 1; Cd14 = monocyte differentiation antigen CD14; Scara1 = scavenger receptor class A type I)
Our results suggest that LPA-enhanced foam cell formation is mediated by LPA1/3 -AKT activation and subsequent SRBI expression.
Lysophosphatidic acid-LPA1 signaling is critically required for septation during alveolarization.
Data show that lysophosphatidic acid receptor 1 (LPA1)-green fluorescent proteins can be used to directly quantify the running-induced increase in precursor proliferation.
Results suggest a relevant role for the Lysophosphatidic acid/Lysophosphatidic acid receptor 1 signaling system in alcoholism. In addition, the LPA1-null mice emerge as a new model for genetic vulnerability to excessive alcohol drinking
Findings describe a functional role for lysophosphatidic acid 1 receptor in the regulation of oligodendrocyte differentiation and myelination in the central nervous system.
Data show that lysophosphatidic acid (LPA) induces phosphorylation of trkA receptor (TrkA) through lysophosphatidic acid receptor 1 (LPA1) binding to TrkA
LPA receptor has a role in bone loss in ovariectomized mice, but the favorable effect of its inhibition on bone remodeling is less general than hypothesized
These findings suggest that tumor and stromal LPA receptors, in particular LPA1 and LPA5, play different roles in invasion and the seeding of metastasis
LPA1 receptor is involved in emotional behaviors and in the anatomical integrity of the corticolimbic circuit, the deregulation of which may be a susceptibility factor for anxiety disorders.
These results suggest that Ile325, Tyr85, and Leu87 within LPA1 are essential for LPA1 protein properly folding in the ER.
These results suggest that LPA1 receptor-mediated amplification of spinal LPA production is required for the development of paclitaxel-induced neuropathic pain.
these results demonstrate that LPA1 is essential for in vitro and in vivo osteoclast activities.
Ultrastructural analyses of peripheral nerves in mouse null-mutants for LPA1 showed delayed schwann cell-to-axon segregation, polyaxonal myelination by single schwann cells, and thinner myelin sheaths.
expression is lower in epithelial cells than in stromal cells of the endometrium
Lysophosphatidic acid stimulates PGE(2) production, cell viability, and intracellular calcium ion mobilization in cultured stromal endometrial cells via Ki16425-sensitive LPA1 receptors.
the ATX-LPA-LPAR axis is a critical regulator of embryonic vascular development that is conserved in vertebrates
LPA(1) is necessary for lymphatic vessel formation during embryonic development in zebrafish.
The integral membrane protein encoded by this gene is a lysophosphatidic acid (LPA) receptor from a group known as EDG receptors. These receptors are members of the G protein-coupled receptor superfamily. Utilized by LPA for cell signaling, EDG receptors mediate diverse biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Two transcript variants encoding the same protein have been identified for this gene
endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 2
, lysophosphatidic acid receptor 1
, lysophosphatidic acid receptor 1-like
, LPA receptor 1
, lysophosphatidic acid receptor Edg-2
, ventricular zone gene 1
, G-protein coupled receptor 26
, clone 4.9
, endothelial differentiation lysophosphatidic acid G-protein-coupled receptor 2
, endothelium differentiation gene 2