Peroxisome Proliferator-Activated ReceptorγRegulates the Expression of Lipid Phosphate Phosphohydrolase 1 in Human Vascular Endothelial Cells

Abstract

Lipid phosphate phosphohydrolase 1 (LPP1), a membrane ectophosphohydrolase regulating the availability of bioactive lipid phosphates, plays important roles in cellular signaling and physiological processes such as angiogenesis and endothelial migration. However, the regulated expression of LPP1 remains largely unknown. Here, we aimed to examine a role of peroxisome proliferator-activated receptor γ (PPARγ) in the transcriptional control of LPP1 gene expression. In human umbilical vein endothelial cells (HUVECs), quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) demonstrated that activation of PPARγ increased the mRNA level of LPP1. Chromatin immunoprecipitation assay showed that PPARγ binds to the putative PPAR-responsive elements (PPREs) within the 5′-flanking region of the human LPP1 gene. Genomic fragment containing 1.7-kilobase of the promoter region was cloned by using PCR. The luciferase reporter assays demonstrated that overexpression of PPARγ and rosiglitazone, a specific ligand for PPARγ, could significantly upregulate the reporter activity. However, site-directed mutagenesis of the PPRE motif abolished the induction. In conclusion, our results demonstrated that PPARγ transcriptionally activated the expression of LPP1 gene in ECs, suggesting a potential role of PPARγ in the metabolism of phospholipids.

Nuciferine ameliorates hepatic steatosis in high‐fat diet/streptozocin‐induced diabetic mice through a PPARα/PPARγ coactivator‐1α pathway

“…PPARα transactivation was determined using a luciferase reporter pGL3 vector containing three peroxisome proliferator response elements (PPRE X3-TK-LUC) as previously described (Huang et al, 2014). When the cells reached the density of 60%, pcDNA3.1 vector containing PPARα expression plasmid (0.9 μg), reporter plasmid PPRE X3-TK-LUC (0.3 μg) and pRSV-gal (0.1 μg, a plasmid expressing β-galactosidase) were transfected into HepG2 cells using Lipofectamine 2000.…”

Peroxisome proliferator-activated receptor γ mediates porcine placental angiogenesis through hypoxia inducible factor-, vascular endothelial growth factor- and angiopoietin-mediated signaling

“…Peroxisome proliferator-activated receptor (PPAR)-γ belongs to the superfamily of nuclear receptors, and is a ligand-activated transcription factor predominantly expressed in adipose tissue and endothelial cells ( 18 , 19 ). PPARγ has been implicated in placentation in mice, as PPARγ −/− embryos exhibit severe impairments in placental vascularization, leading to increased mortality ( 20 , 21 ).…”

Mechanisms of lipid metabolism promoted by berberine via peroxisome proliferator‐activated receptor gamma during in vitro maturation of porcine oocytes

“…Overexpression of PPARG in the human L02 hepatic cell line significantly reduced intracellular and extracellular cholesterol levels by regulating 3-hydroxy-3-methylglutaryl-CoA (HMGCSR) reductase/steroid regulatory element binding transcription factor 2 (SREBF2)-mediated biosynthesis, cytochrome P450 family 7 subfamily A member 1 (CYP7A1)-mediated biosynthesis, ATP-binding cassette subfamily G member 5 (ABCG5)/ATP-binding cassette subfamily G member 8 (ABCG8)-mediated efflux, and other pathways (Han et al, 2018). PPARG can negatively regulate the expression of lipid phosphate phosphohydrolase 1 (LPP1) to inhibit lipolysis in human vascular endothelial cells (Huang et al, 2014). Carvone improved energy metabolism in mice fed a high-fat diet by reducing the expression of PPARG, including reducing hepatic steatosis and body weight and improving blood glucose and insulin resistance (Wu et al, 2019).…”