Indoxyl sulfate stimulates angiogenesis by regulating reactive oxygen species production via CYP1B1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA547986 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9228751.fastq.gz | Fastqsanger.gz | |||
| SRR9228752.fastq.gz | Fastqsanger.gz | |||
| SRR9228753.fastq.gz | Fastqsanger.gz | |||
| SRR9228754.fastq.gz | Fastqsanger.gz | |||
| SRR9228755.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
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:Indoxyl sulfate (IS) is an accumulative protein-bound uremic toxin found in patients with kidney disease. It is reported that IS impairs the vascular endothelium, but a comprehensive overview of all mechanisms active in IS-injury currently remains lacking. Here we performed RNA sequencing in human umbilical vein endothelial cells (HUVECs) after IS or control medium treatment and identified 1293 genes that were affected in a IS-induced response. Gene enrichment analysis highlighted pathways involved in altered vascular formation and cell metabolism. We confirmed these transcriptome profiles at the functional level by demonstrating decreased viability and increased cell senescence in response to IS treatment. In line with the additional pathways highlighted by the transcriptome analysis, we further could demonstrate that IS exposure of HUVECs promoted tubule formation as shown by the increase in total tubule length in a 3D HUVECs/pericytes co-culture assay. Notably, the pro-angiogenic response of IS and increased ROS production were abolished when CYP1B1, one of the main target genes that was highly upregulated by IS, was silenced. This observation indicates IS-induced ROS in endothelial cells is CYP1B1-dependent. Taken together, our findings demonstrate that IS promotes angiogenesis and CYP1B1 is an important factor in IS-activated angiogenic response.
| S-EPMC6723868 | biostudies-literature
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.
2014-01-01 | GSE34259 | GEO
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: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:Long non-coding Rnas (lncRNAs) can act as oncogenes or tumor suppressors to regulate cancer development. We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with the prognosis of patients. Lentiviral vectors were used to overexpress CYP1B1-AS1 in MCF7 cells, and the target proteins bound to CYP1B1-AS1 were detected by pulldown assay and mass spectrometry. The function of CYP1B1-AS1 is unknown. Our study revealed the molecular mechanism of CYP1B1-AS1 inhibiting breast cancer proliferation in breast cancer, and provided a new strategy for the treatment of breast cancer targeting lncRNA.
2023-10-24 | PXD037317 | Pride
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: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:Chronic kidney disease (CKD) is associated with a substantial increased risk of cardiovascular disease. There is growing evidence that uremic metabolites, which accumulate in the blood with CKD, have detrimental impacts on endothelial cell health and function. However, the molecular mechanisms by which uremic metabolites negatively impact endothelial cell biology are not fully understood. In this study, activation of the aryl hydrocarbon receptor (AHR) via indoxyl sulfate, a known uremic metabolite, was found to impair endothelial cell tube formation and proliferation but not migratory function. Moreover, aortic ring cultures treated with indoxyl sulfate also exhibited decreased sprouting and high AHR activation. Next, genetic knockdown of the AHR using shRNA was found to rescue endothelial cell tube formation, proliferation, and aortic ring sprouting. Similarly, pharmacological AHR antagonism using resveratrol and CH223191 were also found to rescue angiogenesis in cell and aortic ring cultures. Finally, a constitutively active AHR (CAAHR) vector was generated and used to confirm AHR-specific effects. Expression of the CAAHR recapitulated the impaired tube formation and proliferation in cultured endothelial cells and decreased sprouting in aortic ring cultures. Taken together, these data define the impact of AHR activation on angiogenesis and highlight the potential for therapeutic AHR antagonists, which may improve angiogenesis in the context of CKD and cardiovascular disease.
| S-EPMC7948007 | biostudies-literature
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