It is generally thought that the large heterogeneity of human HDL confers antiatherogenic properties; however, the mechanisms governing HDL biogenesis and speciation are complex and poorly understood. Here, we show that incubation of exogenous apolipoprotein A-I (apoA-I) with fibroblasts, CaCo-2, or CHO-overexpressing ABCA1 cells generates only alpha-nascent apolipoprotein A-I-containing partic...

OBJECTIVE Scleroderma (systemic sclerosis [SSc]), is characterized by progressive multiorgan fibrosis. We recently implicated lysophosphatidic acid (LPA) in the pathogenesis of pulmonary fibrosis. The purpose of the present study was to investigate the roles of LPA and two of its receptors, LPA₁ and LPA₂, in dermal fibrosis in a mouse model of SSc. METHODS Wild type (WT), and LPA₁-knockout (K...

Lysophosphatidic acid (LPA) is an important intercellular signaling molecule involved in a myriad of biological responses. Elevated concentrations of LPA are present in the ascites and plasma of ovarian cancer patients suggesting a role for LPA in the pathophysiology of ovarian cancer. We have demonstrated previously that oleoyl (18:1) LPA at concentrations present in ascites induces the secret...

The ability of cancer cells to invade and metastasize is the major cause of death in cancer patients. Autotaxin (ATX) is a secreted lysophospholipase whose level of expression within tumors correlates strongly with their aggressiveness and invasiveness. ATX is the major enzyme involved in the production of lysophosphatidic acid (LPA), a phospholipid that is known to act mostly through its three...

BACKGROUND AND AIMS Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an importan...

PURPOSE Although previous studies have demonstrated that hypoxia induces retinal ganglion cell (RGC) apoptosis and that transient retinal ischemia upregulates the expression of lysophosphatidic acid (LPA) receptors, it remains to be determined whether LPA(1) receptor mediates RGC degeneration during retinopathy of prematurity (ROP). By using an immortalized RGC line (RGC-5), primary neonatal RG...

Lysophosphatidic acid (LPA) is an efficient, bioactive phospholipid involved in various biological processes. In this study, LPA-induced connective tissue growth factor (CTGF/CCN2) expression and the underlying mechanisms were investigated using the MC3T3-E1 cell line. The MC3T3-E1 cells were stimulated with an inhibitor of LPA receptors, an activator and inhibitor of protein kinase C (PKC) and...

The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) biosynthesis. LPA(1) receptor activation causes demyelination and sprouting of dorsal root fibers, leading to an induction of synaptic reorganization underlying allodynia, in which innocuous (tactile) stimuli cause intense pain. The LPA(1) signal also initiates the up-regulation of Ca(v)α2δ1 in dors...

Lysophosphatidic acid (LPA) acts through high-affinity G protein-coupled receptors to mediate a plethora of physiological and pathological activities associated with tumorigenesis. LPA receptors and autotaxin (ATX/LysoPLD), the primary enzyme producing LPA, are aberrantly expressed in multiple cancer lineages. However, the role of ATX and LPA receptors in the initiation and progression of breas...

Lysophosphatidic acid (LPA), the simplest of the water-soluble phospholipids, can evoke various biological responses. The present study examined the activity of LPA to induce plasma exudation and histamine release in mice. Plasma exudation was assessed by extravasation of Evans blue. Subcutaneous administration of LPA (1 - 100 microg/site) led to increased plasma exudation in the skin. The LPA-...