Study of the effect on indoxyl sulfate on endothelial gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34259 | GEO | 2014/01/01
SECONDARY ACCESSION(S): PRJNA149745
REPOSITORIES: GEO
Similar Datasets
Project description:The aim of this study is to determine the molecular mechanism by which indoxyl sulfate acts on endothelial cells. Endothelial cells (HUVECs) were incubated with medium containing indoxyl sulfate at concentration found in chronic kidney disease patients (1mM). Since indoxyl sulfate is a potassium salt, control medium contains KCl at 1mM. Cells were incubated during four hours in presence of indoxyl sulfate or KCl. Seven biological replicates were obtained for these two conditions. To understand how uremic solutes participate in endothelial dysfunction and cardiovascular complications of chronic kidney disease patients
2014-01-01 | E-GEOD-34259 | biostudies-arrayexpress
Project description:Indoxyl sulfate (IS) is a uremic toxin and ligand of the aryl-hydrocarbon receptor (Ahr), a transcriptional regulator. Elevated serum IS may contribute to the progression of kidney disease. Therefore, we assessed mouse podocyte damage mediated by IS. Ahr was predominantly localized to the podocyte nucleus in vivo and in vitro. In isolated glomeruli, IS-exposure for 2 – 24 h induced Cyp1a1 expression, the most sensitive biomarker of Ahr activation. Mice exposed to IS for 4–8 weeks exhibited microalbuminuria, and mild glomerular injury characterized by ischemic changes, partial podocyte foot process effacement, as well as vascular and tubulointerstitial damage. Chronically IS-exposed kidneys exhibited decreased mRNA, decreased protein levels, and altered staining patterns for podocin, synaptopodin, and non-muscle myosin IIA (Myh9). Immortalized podocytes, upon differentiation, exhibited Ahr nuclear translocation beginning 30 min after 1 mM IS-exposure. At 2 h, there was a dose-dependent decrease in podocyte mRNA expression of WT1, Podxl, Snypo, Myh9, Actn4, and Cd2ap. After 24 h of exposure to IS, podocytes were smaller, had fewer actin/Myh9 fibers, and decreased viability. Ahr-RNAi decreased mRNA expression of podocyte-specific proteins and inhibited Cyp1a1 induction by IS-exposure. Combinations of Ahr-RNAi and IS-exposure further decreased Myh9 expression. In immortalized human podocytes, IS treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. Thus, chronic IS-exposure causes glomerular damage by activating Ahr, altering podocyte function, differentiation, and morphology, and inducing a pro-inflammatory phenotype. Podocyte cells treated with Indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand, mediates progressive glomerular disease by damaging podocytes Human podocyte cell line treated with or without 3-Indoxyl sulfate (1mM/0.1%DMSO) in three replications
2014-10-14 | E-GEOD-51834 | biostudies-arrayexpress
Project description:End-stage renal disease (ESRD) is the final stage of chronic kidney disease, which is increasingly prevalent worldwide and is associated with the progression of cardiovascular disease (CVD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), major uremic toxins, are major risk factors involved in the pathology of CVD via adverse effects on endothelial cells and immune cells. Thus, transcriptomic overview of uremic toxin-mediated genes in immune cells of ESRD patients is critical, but not yet fully known. We investigated the alteration of gene expressions and biological pathways mediated by major uremic toxins, in ESRD patients monocytes, via microarray analysis. To explore uremic toxin-related transcriptional profiling in ESRD patient-derived monocytes, purified monocytes from healthy controls were treated with IS or PCS for 24 hr, followed by conducting microarray on these samples.
2020-07-30 | GSE155325 | GEO
Project description:Vascular calcification contributes to high cardiovascular mortality in chronic kidney disease (CKD) patients. An association between the uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) and cardiovascular disease has been suggested. This study provides strong etiological evidence for indoxyl sulfate and p-cresyl sulfate as major contributors to vascular calcification in chronic kidney disease patients. Continuous exposure to indoxyl sulfate or p-cresyl sulfate in rats with chronic kidney disease promotes moderate to severe calcification in the aorta and peripheral vessels. Unbiased proteomic analyses of arterial samples coupled to functional bioinformatics annotation analysis revealed that calcification events were associated with acute phase response signaling, coagulation and glucometabolic signaling pathways, while escape from toxin-induced calcification was linked with liver X receptors and farnesoid X/liver X receptor signaling pathways. Activation of inflammation and coagulation pathways in the arterial wall plays a pivotal role in toxin-induced calcification and strongly associates with hyperglycemia and insulin resistance. These findings reveal new perspectives to establish novel therapeutic targets to prevent, halt progression or cure vascular calcification.
2019-06-13 | PXD012582 | Pride
Project description:Introduction: Indoxyl sulfate (IS) is an accumulated protein-bound uremic toxin found in patients with kidney disease. Although it is known that IS impairs the vascular endothelium, the precise underlying mechanism remains unclear. Methods: We performed RNA sequencing in human umbilical vein endothelial cells (HUVECs) that were treated with either IS or control medium. Gene enrichment analyses were performed based on differentially expressed genes. We further examined the main enriched biological processes at the functional level. Results: We identified 1,293 genes that were affected in IS-treated HUVECs when compared to control and gene enrichment analysis indicated altered vascular formation and cell metabolism. We observed decreased viability and increased cell senescence due to IS treatment at the functional level. Furthermore, we demonstrated that IS exposure of HUVECs promoted angiogenesis as shown by the increase in total tubule length in a 3D HUVECs/pericytes co-culture assay. We also observed an increase in ROS production in IS-treated endothelial cells. Notably, the pro-angiogenic response of IS and the increased ROS production were abolished when CYP1B1, one of the main target genes that was upregulated by IS, was silenced. Conclusion: IS promotes angiogenesis and CYP1B1 is an important factor in IS-activated angiogenic response.
2019-09-18 | GSE132410 | GEO
Project description:Transcriptional profiling of human monocytes treated with indoxyl sulfate (IS) or p-cresyl sulfate (PCS)
| PRJNA649416 | ENA
Project description:Indoxyl sulfate (IS) is a uremic toxin and ligand of the aryl-hydrocarbon receptor (Ahr), a transcriptional regulator. Elevated serum IS may contribute to the progression of kidney disease. Therefore, we assessed mouse podocyte damage mediated by IS. Ahr was predominantly localized to the podocyte nucleus in vivo and in vitro. In isolated glomeruli, IS-exposure for 2 – 24 h induced Cyp1a1 expression, the most sensitive biomarker of Ahr activation. Mice exposed to IS for 4–8 weeks exhibited microalbuminuria, and mild glomerular injury characterized by ischemic changes, partial podocyte foot process effacement, as well as vascular and tubulointerstitial damage. Chronically IS-exposed kidneys exhibited decreased mRNA, decreased protein levels, and altered staining patterns for podocin, synaptopodin, and non-muscle myosin IIA (Myh9). Immortalized podocytes, upon differentiation, exhibited Ahr nuclear translocation beginning 30 min after 1 mM IS-exposure. At 2 h, there was a dose-dependent decrease in podocyte mRNA expression of WT1, Podxl, Snypo, Myh9, Actn4, and Cd2ap. After 24 h of exposure to IS, podocytes were smaller, had fewer actin/Myh9 fibers, and decreased viability. Ahr-RNAi decreased mRNA expression of podocyte-specific proteins and inhibited Cyp1a1 induction by IS-exposure. Combinations of Ahr-RNAi and IS-exposure further decreased Myh9 expression. In immortalized human podocytes, IS treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. Thus, chronic IS-exposure causes glomerular damage by activating Ahr, altering podocyte function, differentiation, and morphology, and inducing a pro-inflammatory phenotype. Podocyte cells treated with Indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand, mediates progressive glomerular disease by damaging podocytes
2014-10-14 | GSE51834 | GEO
Project description:The expression profile of natural isolate of S. cerevisiae carrying different copy of CUP2 were compared under cooper sulfate stress The gene expression profiles of natural isolate of S.cerevisiae(EC9-7), EC9-7 cup2∆ and Ec9-7 cup2∆cup2∆ strains under YPD with 1mM copper sulfate for 1h and rich medium(YPD) were compared.
2011-08-25 | E-GEOD-31661 | biostudies-arrayexpress
Project description:Indoxyl sulfate stimulates angiogenesis by regulating reactive oxygen species production via CYP1B1
| PRJNA547986 | ENA
Project description:Introduction: Cardiovascular pathology is the main cause of death in patients with chronic kidney disease (CKD). CKD is associated with the accumulation of uremic toxins in the bloodstream due to their difficult elimination by renal substitution therapy. Indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of patients with CKD. We conducted an in vitro study to assess the mechanisms underlying IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We studied not only endothelial cells but also their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo. Methods: EVs were characterized using nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry, and their tetraspanin expression was evaluated to confirm their identity as EVs. Subsequently, mass spectrophotometry of the protein lysates of cells and EVs was performed, followed by Gene Set Enrichment Analysis to identify the principal altered pathways. Additionally, qPCR and proliferation analyses were performed to confirm proteomic results. Results: Proteomic analysis of endothelial cells revealed that IS causes an increase in proteins related to adipogenesis, inflammation, and xenobiotic metabolism and a decrease in proliferation via mTOR. Inflammation due to TNF signaling via NFкB was confirmed by an increase in the expression of the target genes IL-6, MCP-1, and ICAM-1. Concerning EVs, extracellular matrix elements were reduced, and myogenesis genes were downregulated in response to UV irradiation and inflammation. Fatty acid metabolism also seemingly increases, which, along with adipogenesis and inflammation observed in cells, could be related to atherosclerosis. Conclusions: Endothelial cells treated with IS had more proteins related to adipogenesis, inflammation, and xenobiotic metabolism and fewer associated with proliferation. Furthermore, EVs from cells treated with IS may mediate endothelial dysfunction, since they present fewer extracellular matrix elements, myogenesis and inflammatory factors, and proteins downregulated in response to UV radiation.
2024-11-29 | PXD050628 | Pride