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HUVECs with endogenous or overexpressed GPR4 treated with pH 8.4 (control) or pH 6.4 for 5 h

ABSTRACT: Acidic tissue microenvironment is commonly found in a variety of pathophysiological conditions. GPR4 is a proton-sensing G protein-coupled receptor that is fully activated by acidic extracellular pH but has lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To determine the effects of GPR4 activation by acidosis on vascular endothelial cells, we examined the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. HUVEC with endogenous or overexpressed GPR4 level (designated as HUVEC/Vector & HUVEC/GPR4 cells). Two treatment conditions: pH 6.4 vs. pH 8.4 for 5 h. Biological replicates: 4 HUVEC/Vector replicates (pH6.4 vs pH 8.4), and 4 HUVEC/GPR4 replicates (pH6.4 vs pH 8.4).

ORGANISM(S): Homo sapiens

SUBMITTER: Lixue Dong

PROVIDER: E-GEOD-40060 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.

Dong Lixue L Li Zhigang Z Leffler Nancy R NR Asch Adam S AS Chi Jen-Tsan JT Yang Li V LV

PloS one 20130416 4

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH ...[more]

PMID: 23613998

Similar Datasets

HUVECs with endogenous or overexpressed GPR4 treated with pH 8.4 (control) or pH 6.4 for 5 h

Project description:Acidic tissue microenvironment is commonly found in a variety of pathophysiological conditions. GPR4 is a proton-sensing G protein-coupled receptor that is fully activated by acidic extracellular pH but has lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To determine the effects of GPR4 activation by acidosis on vascular endothelial cells, we examined the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4.

2013-04-25 | GSE40060 | GEO

microarray analysis in SREBP2-knockdown cells under low pH (pH 6,8) culture conditions

Project description:The conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification.

2017-01-25 | GSE93980 | GEO

Gene array analysis of Human Umbilical Vein Endothelial Cells (HUVEC) transduced with lentivirus containing cDNA of NKX2,5 or GATA4 or GFP.

Project description:The aim of this study was to induce cardiomyogenic conversion of Human Umbilical Vein Endothelial Cells (HUVEC ) by triggering ectopic expression of the cardiac transcription factors Nkx2.5 and GATA4. Cells were cultured without cell myocardial co-culture system and transduced with lentivirus containing coding sequence of Nkx2.5, GATA4 or GFP as control. Cells were cultured in the EBM-2/ EGM-2 medium, 12 days before microarray analysis. We report in this study that over-expression of NKX2.5 and GATA4 in HUVECs stimulates the expression of some specific genes important in the cardiomyogenic differentiation process, leading to partial switch of these cells from the endothelial to the myocardial course. 12 arrays were analysed. Three competitive hybridizations to the arrays were performed in duplicate using each time, two dye-swap following this experimental design: AWA065 : CY5 (HUVEC+NKX2,5) / CY3 (HUVEC) AWA067 : CY5 (HUVEC) / CY3 (HUVEC+NKX2,5) AWA075 : CY5 (HUVEC+NKX2,5) / CY3 (HUVEC) AWA076 : CY5 (HUVEC) / CY3 (HUVEC+NKX2,5) AWA068 : CY5 ((HUVEC) / CY3 (HUVEC+GATA4) AWA070 : CY5 (HUVEC+GATA4) / CY3 ((HUVEC) AWA073 : CY5 (HUVEC+GATA4) / CY3 ((HUVEC) AWA002 : CY5 ((HUVEC) / CY3 (HUVEC+GATA4) AWA066 : CY5 (HUVEC) / CY3 (HUVEC+NKX2.5+GATA4) AWA069 : CY5 (HUVEC+NKX2.5+GATA4) / CY3 (HUVEC) AWA071 : CY5 (HUVEC+NKX2.5+GATA4) / CY3 (HUVEC) AWA074 ; CY5 (HUVEC) / CY3 (HUVEC+NKX2.5+GATA4)

2012-04-20 | E-GEOD-37459 | biostudies-arrayexpress

Identification of acidic extracellular pH-modulated genes

Project description:To investigate the genes that are modulated by acidic extracellular pH, we treated the mouse B16-BL6 cells with acidic medium and then analyzed them comprehensively by cDNA microarray.

2024-09-09 | GSE276124 | GEO

Mycobacterium tuberculosis transcriptional responses to acidic pH and carbon source

Project description:The purpose of this study was to examine how Mtb integrates acidic pH and available carbon sources as environmental cues to regulate its metabolism and growth rate. RNA-seq transcriptional profiling of M. tuberculosis growing at acidic or neutral pH, in pyruvate or glycerol, was examined. These studies identified carbon source-dependent and -independent pH-dependent adaptations.

2014-07-07 | GSE52020 | GEO

The Rfg1 and Bcr1 transcription factors regulate acidic pH-induced filamentous growth in Candida albicans

Project description:To investigate the function of Rfg1 in sensing acidic pH and regulating filamentation in C. albicans, we performed the global gene expression profile analysis of WT and rfg1/rfg1 mutant.We reveal that Rfg1 is an essential acidic pH sensor in C. albicans. Rfg1 regulates filamentous growth in acidic pH condition via co-regulation of Rim101-Phr1 pathway, cAMP signaling pathway,and the transcription factors Bcr1, Efg1, Flo8, and Hgc1.

2023-03-24 | GSE227654 | GEO

pH regulates white-opaque switching and sexual mating in Candida albicans

Project description:As a successful commensal and pathogen of humans, Candida albicans encounters a wide range of environmental changes. Among them, ambient pH is an important factor, which changes frequently and affects many biological processes in this species. The ability to adapt to pH changes is tightly linked with pathogenesis and morphogenesis. In this study, we report that pH has a profound effect on white-opaque switching and sexual mating in C. albicans. Acidic pHs promote white-to-opaque switching but repress sexual mating of opaque cells. The cAMP signaling and Rim101-mediated pH sensing pathways are involved in the regulation of pH-regulated white-opaque switching. Interestingly, white and opaque cells of the cyr1/cyr1 mutant, which is defective in producing cAMP, show distinct growth defects under acidic and alkaline conditions. Phr2 could play a major role in acidic pHs-induced opaque cell formation. We further discover that acidic pH conditions repress sexual mating due to the failure of activation of the Ste2-mediated a-pheromone response pathway. The effects of pH changes on phenotypic switching and sexual mating could be a balance behavior between host adaptation and sexual reproduction.

2015-12-30 | GSE67101 | GEO

Transcriptome data of Penicillium citrinum regulated by pH

Project description:Penicillium citrinum X9-4, which was isolated from infected grapes by our laboratory, produced the highest amount of OTA at pH 5 in culture media, and toxin-production was restrained under acidic environment (pH 3). It revealed the possible mechanism of OTA biosynthesis and metabolic regulation in P. citrinum by transcriptomics, and investigated the reason of OTA biosynthesis was restrained in P. citrinum when cultured under acidic environment.

2017-08-15 | GSE102600 | GEO

Transcriptomic analysis of Mtb H37Rv and MtbΔwhiB3 at pH 4.5

Project description:Since WhiB3 expression was shown to be maximally upregulated at pH 4.5 and MtbΔwhiB3 was shown to be defective in survival in Ph 4.5, we did microarray at pH 4.5 so as to study comprehensive role of WhiB3 in regulating gene expression at acidic Ph

2015-12-02 | GSE61579 | GEO

Response of Candida glabrata to low pH

Project description:To examine the role of a glycosylphosphatidylinositol-linked aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata, transcriptional profiling analysis was carried out on wild-type and Cgyps1∆ cells grown in YNB medium (pH 5.5) and in YNB medium adjusted to pH 2.0. Genes involved in carbohydrate and amino acid metabolism, protein folding and stress response pathways were found to be differentially regulated in response to acidic environment in both the strains. To examine the role of a glycosylphosphatidylinositol-linked aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata, transcriptional profiling analysis was carried out on wild-type and Cgyps1∆ delta cells grown in YNB medium (pH 5.5) and in YNB medium adjusted to pH2.0. Genes involved in carbohydrate and amino acid metabolism, protein folding and stress response pathways were found to be differentially regulated in response to acidic environment in both the strains

2011-01-10 | GSE24267 | GEO

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