RNA-seq of human brain endothelial cells treated with Nrf2 activator RTA-404
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB87670 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Systemic inflammation can lead to a compromised blood-brain barrier (BBB) and neuro-inflammation, with acute consequences such as delirium, and long-lasting deleterious effects including cognitive decline and the exacerbation of neurodegenerative disease progression. Previous studies have shown beneficial roles of Nrf2 in the development and homeostastis of endothelial cells, an integral component of the BBB. We performed RNA-seq on human brain endothelial cells, in a control condition and treated with RTA-404 (CDDO-TFEA), a potent stimulator of Nrf2.
2025-03-27 | E-MTAB-14978 | biostudies-arrayexpress
Project description:Systemic inflammation can lead to neuroinflammation with acute consequences such as delirium and long-lasting deleterious effects including cognitive decline and the exacerbation of neurodegenerative disease progression. Here we show that transcription factor Nrf2 controls brain endothelial cell homeostasis and barrier strength. We found that peripheral inflammation caused infiltration of macrophages, microglial activation and inflammatory reactive astrogliosis, all of which could be prevented by RTA-404, an activator of the transcription factor Nrf2 and close structural relative of the recently FDA-approved Nrf2 activator RTA-408 (Omaveloxolone). To identify the key cellular mediator(s), we generated an endothelial cell-specific Nrf2 knockout mouse. Strikingly, the effects of RTA-404 on brain endothelial activation and downstream neuroinflammatory events were abolished by endothelial cell-specific Nrf2 deletion. This places endothelial cell Nrf2 as a peripherally accessible therapeutic target to reduce the CNS-adverse consequences of systemic inflammation
2025-05-02 | PXD063497 | Pride
Project description:Targeting T-cells has emerged as a promising therapeutic strategy for treating inflammatory diseases. Triterpenoids, classified as antioxidant inflammatory modulator (AIM) compounds, are known to influence immune cell functions. RTA-408 is an AIM drug that was approved last year for the treatment of neurological disorders. In this study, we demonstrate the anti-inflammatory effects of RTA-408, on both mouse and human T-cells. At picomolar concentrations, RTA-408 robustly induces NRF2 activation in T-cells and reduces T-cell activation, proliferation, and cytokine functions. In in vitro activated CD4 and CD8 T-cells isolated from mice and human blood, we observed a significant decrease in proliferation, and expression of inflammatory cytokine IFN-γ, and cytotoxic granules (perforin and granzyme B). Mechanistically, treatment with RTA-408 significantly suppressed glycolysis and mitochondrial respiration in human T-cells, while increasing the expression of pentose phosphate pathway genes, such as transketolase (TKT) and transaldolase (TALDO). These findings suggest that RTA-408 modulates T-cell metabolism. Furthermore, treatment of circulating T-cells from inflammatory bowel disease (IBD) patients with RTA-408 caused a reduction in expansion and the expression of the inflammatory cytokine IL-17. Our results highlight the therapeutic potential of RTA-408 in treating chronic inflammatory conditions like IBD by modulating T-cell activity.
2025-04-01 | GSE277154 | GEO
Project description:To investigate the functions of NRF2 activation on maturation of hiPSC derived cardiomyocytes, we treated 3D hiPSC derived cardiomyocytes with NRF2 activator CDDO-Me at 0.5 µM for 10 days. Transcriptomic analyse was performed to identify molecular actions of NRF2 activation.
2022-06-08 | GSE205566 | GEO
Project description:EBV Rta is a transcriptional activator that functions to disrupt EBV latency in cells of epithelial origin. This series of experiment is to identify host genes that are moduated by the expression of doxycycline-inducible EBV Rta in HEK293 cells. Designations for the pooled EBV Rta inducible cell lines is 293TetER; pooled luciferase inducible lines is 293TetLuc (control).
2011-05-22 | GSE24585 | GEO
Project description:EBV Rta is a transcriptional activator that functions to disrupt EBV latency in cells of epithelial origin. This series of experiment is to identify host genes that are moduated by the expression of doxycycline-inducible EBV Rta in nasopharyngeal carcinoma cells. Designations for the two EBV Rta inducible cell lines are TW01TetER_cl7 (lower expression level) and TW01TetER_cl19 (higher expression level); for the control line is TW01Tet.
2011-05-22 | GSE24586 | GEO
Project description:KSHV RTA (K-RTA) is a transcriptional activator that functions to disrupt KSHV latency and activates specific sets of viral promoters in the lytic cycle. Structure-function studies indicate that K-RTA possesses a very potent transactivation domain locating at the C-terminus. To further characterize the biological functions of K-RTA, we have established three doxycycline-inducible K-RTA 293 cell lines using RevTRE/Tet-On system (Clontech). Comparing to two control lines in which K-RTA was replaced with luciferase reporter, a total of 88 host genes were identified to be modulated by 24 h doxycycline-induced K-RTA synthesized in 293 cells. Designations for the three K-RTA inducible cell lines are KRta_92, KRta_116 and KRta_124; for the control line is RevTRE_Luc_1.
2010-05-26 | GSE21987 | GEO
Project description:Here we studied the role of oxidized phospholipids in mediating phenotype switching of endothelial cells between quiescent and angiogenic states. Two oxPAPC datasets, a microRNA array and global run-on sequencing (GRO-seq), was combined with Nuclear factor erythroid 2-Related Factor 2 (NRF2) binding model to select candidate miRNAs for further studies. The pre-screening resulted in a selection of miR-106b~25 cluster for further studies. The cluster was shown to be both oxPAPC-responsive and NRF2-regulated, and its diagnostic and prognostic potential was investigated in pericardial fluid samples of heart failure and atherosclerosis patients. As the most abundant member of the cluster in both endothelial cells and pericardial fluid of atherosclerosis patients, miR-93-5p was selected for more detailed studies. RNA-seq from miR-93 overexpressing cells revealed significant changes in pathways related to angiogenesis. Together with NRF2, miR-93 was shown to control endothelial plasticity through regulation of the key players, namely Krüppel-like factor 2 (KLF2) for quiescence, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) for glycolysis, and Vascular Endothelial Growth Factor A (VEGFA), Forkhead box protein O1 (FOXO1) and MYC proto-oncogene protein (MYC) for growth and proliferation.The findings show that NRF2 and miR-93 control the activity of endothelial cells and mediate the effects of oxPAPC on endothelial activation, collectively providing novel mechanisms for the control of endothelial plasticity and oxPAPC response.
2017-11-01 | GSE103530 | GEO
Project description:Sinorhizobium medicae 404 Resequencing
| PRJNA499403 | ENA
Project description:EBV Rta is a transcriptional activator that functions to disrupt EBV latency in cells of epithelial origin. This series of experiment is to identify host genes that are moduated by the expression of doxycycline-inducible EBV Rta in nasopharyngeal carcinoma cells. Designations for the two EBV Rta inducible cell lines are TW01TetER_cl7 (lower expression level) and TW01TetER_cl19 (higher expression level); for the control line is TW01Tet. All the three inducible cell lines were grown to log-phase before doxycycline induction. Same number of cells from the three cell lines were treated with doxycycline for 24 h. Total RNAs from the three samples were extracted and subjected to microarray analysis (Affymetrix Human Gene 1.0 ST Array , n=33,297). We sought to identify genes up- or down-regulated in the two doxycycline-treated EBV Rta cells, but not in the treated control cells.
2011-05-22 | E-GEOD-24586 | biostudies-arrayexpress