HUVECs with endogenous or overexpressed GPR4 treated with pH 8.4 (control) or pH 6.4 for 5 h
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40060 | GEO | 2013/04/25
SECONDARY ACCESSION(S): PRJNA172639
REPOSITORIES: GEO
Similar Datasets
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. 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).
2013-04-25 | E-GEOD-40060 | biostudies-arrayexpress
Project description:This study is to identify downstream genes regulated by STAT3 in response cytosolic acidification. Dysregulated intracellular pH is emerging as a hallmark of cancer. In spite of their acidic environment, cancer cells maintain alkaline intracellular pH (≥7.4) that promotes cancer progression by inhibiting apoptosis and increasing glycolysis, cell growth, migration and invasion. Here, we identify signal transducer and activator of transcription 3 (STAT3) as a key player in the maintenance of alkaline cytosolic pH. STAT3 associates with the vacuolar H+-ATPase on lysosomal membranes in a coiled coil domain-dependent manner and increases its activity in living cells and in vitro. Accordingly, STAT3 depletion disrupts intracellular proton equilibrium by decreasing and increasing cytosolic and lysosomal pH, respectively. This dysregulation can be reverted by reconstitution with wild type STAT3 as well as STAT3 mutants unable to activate target genes (Tyr-705-Phe and DNA binding mutant) or to regulate mitochondrial respiration (Ser-727-Ala). Upon cytosolic acidification, phospho-Tyr-705-STAT3 is rapidly dephosphorylated, transcriptionally inactivated and further recruited to lysosomal membranes to reestablish intracellular proton equilibrium and to enhance cell survival. These data reveal STAT3 as a regulator of intracellular pH, and vice versa intracellular pH as a regulator of STAT3 localization and activity.
2018-01-03 | GSE108495 | GEO
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
Project description:OGR1 is a pH-sensing G-protein coupled receptor involved in intestinal homeostasis and inflammation Proton activation of OGR1 increases barrier function in Caco2 cells Microarray profiling was performed on OGR1 stable overexpressing Caco-2 cells during acidic pH shift
2015-08-13 | E-GEOD-60294 | biostudies-arrayexpress
Project description:Trefoil factor family member 2 (Tff2) is significantly involved in intestinal tumor growth in ApcMin/+ mice, which can be used as a human colon cancer model. TFF2, which encodes TFF2 (spasmolytic protein 1) is highly expressed in human cancer tissues, including the pancreas, colon and bile ducts, as well as in normal gastric and duodenum tissues. By contrast, TFF2 exhibits low expression levels in other normal tissues, including the small and large intestine. Furthermore, TFF2 expression has not been detected in DLD-1 cells, a cell line derived from human colon cancer. The trigger of TFF2 expression in normal and tumor cells remains unknown. Highly malignant tumor tissues are characterized by higher temperatures and lower pH (6.2-6.9) than in normal tissues, where the normal pH ranges from 7.2 to 7.4. This microenvironment exacerbates malignancy by promoting the acquisition of cell death resistance, drug resistance and immune escape. Therefore, the present study examined how TFF2 expression is affected in cultured cells that imitate the tumor tissue microenvironment. The incubation temperature was increased from 37 to 40˚C, but no expression of TFF2 was induced. Subsequently, a culture solution with an acidic pH was prepared to simulate the Warburg effect in tumors. TFF2 expression was increased by 42.8- and 5.8-fold in cells cultured in acidic medium at pH 6.5 and 6.8 compared with at pH 7.4, respectively, as determined using the relative quantification method following quantitative polymerase chain reaction. The present study also analyzed fluctuations in the expression levels of genes other than TFF2, under acidic conditions. Acidic conditions upregulated the expression of genes related to cell membranes and glycoproteins, based on the Database for Annotation, Visualization, and Integrated Discovery. In conclusion, TFF2 was highly expressed under acidic conditions, implying that it may have an important function in protecting the plasma membrane from acidic environments in both normal and cancer cells. These findings warrant further investigation of TFF2 as a target of cancer therapy and diagnosis.
2024-02-16 | GSE246091 | GEO
Project description:Metabolic acidosis exacerbates chronic kidney disease, in part, by stimulating renal endothelin production. To determine if acidosis alters expression of other genes, we examined the effect of exposure of MDCK cells to pH 7.4 and pH 7.0 for 24 hours on gene expression using a canine derived microarray. Exposure to this pH stress for 24 hours led to increased expression of 278 genes (2.2% of the transcriptome) by at least two fold and 60 of these (21%) were upregulated by more than 3 fold. On the other hand, 186 genes (1.5% of the transcriptome) were down regulated by at least two fold and 16 of these (9%) were down regulated by 3 fold or more. Ten percent of the genes upregulated by at least three fold encode proteins that are pro-inflammatory cytokines, including colony stimulating factor 2, chemokine ligand 7, chemokine ligand 2 0, chemokine ligand 8, and interleukin 1M-NM-1. Two others encode metallopeptidase . The most highly upregulated gene encodes a protein, lubricin, shown to be important in preventing cartilage damage and in tissue injury or repair.Upregulation of four genes were confirmed by qPCR. Housekeeping genes were not increased. There were a total of three biological replicates, each containing one control (incubated at pH 7.4) and one acidic (pH 7.0) sample, whose RNA were extracted on different dates. Microarray studies performed on these six samples were done in duplicate.
2012-03-27 | E-GEOD-36848 | biostudies-arrayexpress
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
Project description:Chronic metabolic acidosis occurs commonly in patients with diseased kidneys and is linked with progression to renal failure. As renal function declines there is loss of nephron mass and adaptive proximal tubular hypertrophy and hypermetabolism. We have previously demonstrated in an in vitro model of chronic acidosis in porcine LLC-PK1 cells increased ammonia generation (oxidative hypermetabolism) linked with tubular cellular dysfunction and increased markers of oxidative stress. The aim of this study was to determine the effect of chronic acidosis in HK-2 cells on changes in gene and protein expression stimulated by oxidative stress. HK-2 cells were were seeded onto 6 well plates at a density of 4x104 cells/well and cultured for 72 h in growth medium (DMEM/Ham s F12 medium supplemented with 5.5 mM glucose, 2 mM L-glutamine, 5 ug/ml insulin, 5 ug/ml transferrin, 5 ng/ml sodium selenite, 0.4 ug/ml hydrocortisone, 5 ng/ml epidermal growth factor, 100 U/ml penicillin, 100 ug/ml streptomycin, and 10% FCS). The medium was then replaced by growth media buffered to pH 7.4, 7.0 or 6.7 with 12.5 mM bis-Tris and cells were cultured for further 48 h. Media were changed to serum free media (SFM) buffered by 12.5 mM bis-Tris to pH 7.4, 7.0 or 6.7 and cells were harvested and RNA isolated after 24 h. Total RNA was isolated from HK-2 cells on 3 different occasions using Tri-reagent (Sigma, UK) as recommended by the manufacturer's protocol. The RNA from the respective replicate samples were pooled together and the RNA content was measured using RiboGreen RNA Quantitation Reagent (Molecular Probes, Invitrogen, UK). The integrity of the total RNA was verified on a denaturing agarose-formaldehyde gel.
2012-09-11 | E-GEOD-23995 | biostudies-arrayexpress
Project description:Cells were grown in light (R0K0) SILAC media (AthenaES) for 7 days, they were then incubated in light media for 24 hours in respective condition (normoxia neutral (NN) pH: 7.4; hypoxia neutral (HN)1% O2, pH: 7.4; hypoxia acidosis (HA), 1% O2, pH=6) and pulsed with heavy (R10K8) SILAC media (AthenaES) for 16 hr (TMT-pSILAC) following treatment.
2020-09-28 | PXD015643 | Pride
Project description:The aim of the study was to compare the RNA-SEQ profiles of a wild type C. albicans strain (SC5314), a rim101-/- mutant strain (DAY25) and a strain overexpressing RIM101 (CGY1) at both alkaline (7.6) and acidic (4) pH, in order to identify Rim-dependent genes involved in tolerance to antifungals
2018-01-18 | GSE109291 | GEO