Microarray analysis of TFEB-regulated genes in vascular smooth muscle cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138000 | GEO | 2020/11/21
REPOSITORIES: GEO
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Project description:Transcription factro-EB (TFEB) is a master gene for autophagy and lysosome biogenesis We used microarrays to detail the gene expression in TFEB-overexpressing endothelial cells and identified distinct classes of TFEB-regulated genes.
2018-05-01 | GSE108384 | GEO
Project description:How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3 phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognised nuclear export signal (NES). Importantly, GSK3 is inactivated by AKT in response to mTORC2 signalling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle.
2018-10-18 | PXD009677 | Pride
Project description:Lysosomes are at the epicenter of cellular processes critical for inflammasome activation in macrophages, including autophagy and lipid metabolism. Inflammasome activation and IL1-beta secretion are implicated in atherogenesis, ischemic cardiac injury and resultant heart failure; however, little is known about the role of macrophage lysosome function in regulating these processes. We hypothesized that macrophages exhibit lysosome dysfunction in heart failure due to ischemic injury, and that augmentation of macrophage lysosomal biogenesis via macrophage-specific overexpression of transcription factor EB (mf-TFEB) would attenuate ischemic remodeling by modulating macrophage inflammatory responses. In both mice subject to ischemia-reperfusion injury, and human heart tissue from patients with ischemic cardiomyopathy, we find evidence of lysosome insufficiency and autophagic impairment, respectively. Mf-TFEB overexpression significantly attenuated post-IR adverse left ventricular remodeling at 4 weeks without affecting scar size. Mf-TFEB overexpression reduced the relative amounts of pro-inflammatory macrophage populations in the myocardium. RNA sequencing of flow-sorted cardiac macrophages post-IR confirmed that TFEB stimulated a lysosomal transcriptional program in macrophages, and upregulated key targets involved in lysosomal lipid metabolism, which we show are critical for inflammasome suppression. Both TFEB-dependent inflammasome suppression and effects on post-IR remodeling were independent of autophagy. Our findings suggest that TFEB reprograms macrophage lysosomal lipid metabolism to attenuate inflammasome activity and protect against post-ischemic cardiac remodeling and simultaneously shift our understanding of how autophagy and lipid metabolism impact acute inflammation.
2019-11-01 | GSE118463 | GEO
Project description:In order to identify the effects of transcription factor EB (TFEB) overexpression on the liver transcriptome, we performed Affymetrix GeneChip hybridization experiments on injected mice overexpressing TFEB specifically in the liver. For the analysis of the injected mice overexpressing TFEB, total RNA was extracted from the liver of three mice. RNA extracted from the liver of 3 not-injected mice was used as a control.
2013-04-20 | E-GEOD-35015 | biostudies-arrayexpress
Project description:In order to identify the effects of transcription factor EB (TFEB) overexpression on the liver transcriptome, we performed Affymetrix GeneChip hybridization experiments on injected mice overexpressing TFEB specifically in the liver.
2013-04-20 | GSE35015 | GEO
Project description:The transcription factors EB and E3 (TFEB and TFE3) promote lysosomal biogenesis and autophagy in response to a variety of stress conditions. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the ß-coronaviruses family. Recent studies have shown that ß-coronaviruses use lysosomes to egress the cell. The aim of this work is to analyze if ß-coronavirus infection promotes TFEB/3 activation and to evaluate the contribution of these transcription factors to the cellular response upon viral infection.
2023-03-02 | GSE210676 | GEO
Project description:The transcription factors EB and E3 (TFEB and TFE3) promote lysosomal biogenesis and autophagy in response to a variety of stress conditions. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the ß-coronaviruses family. Recent studies have shown that ß-coronaviruses use lysosomes to egress the cell. The aim of this work is to analyze if ß-coronavirus infection promotes TFEB/3 activation and to evaluate the contribution of these transcription factors to the cellular response upon viral infection.
2023-03-02 | GSE210675 | GEO
Project description:To Study the role of mutant Braf V600E and ERK dependent phosphorylation of TFEB in regulation of autophagy and lysosome biogenesis in the context of melanoma growth and metastasis, we used whole geneome RNA-seq to study role TFEB mediated BRAFV600E autophagy regulation.
2019-03-21 | GSE122614 | GEO
Project description:The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
2018-11-20 | GSE88894 | GEO
Project description:The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
2018-11-20 | GSE88895 | GEO