NFAT5/TonEBP controls metabolic adaption and tone of pulmonary vascular smooth muscle cells in the hypoxic lung [normoxia vs hypoxia]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA739162 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:NFAT5/TonEBP controls metabolic adaption and tone of pulmonary vascular smooth muscle cells in the hypoxic lung
| PRJNA739156 | ENA
Project description:NFAT5/TonEBP controls metabolic adaption and tone of pulmonary vascular smooth muscle cells in the hypoxic lung [SMC]
| PRJNA739164 | ENA
Project description:Hypoxia provokes adaptive responses of cells, which ensure their energy supply including the adjustment of the transcriptome to match their metabolism. In this context, we explored the transcriptional impact of nuclear factor of activated T-cells 5 (NFAT5) on the function of vascular smooth muscle cells (VSMC) in the hypoxic lung. Exposure to hypoxia induced a rapid nuclear translocation of NFAT5 in cultured murine VSMCs. SMC-specific ablation of Nfat5 (Nfat5(SMC-/-)) increases the systolic pressure in the right ventricle (RVSP) of the mouse heart and impairs its function upon exposure to hypoxia for 7 and 21 days. Analyses of the transcriptome of the lung revealed a robust increase in the expression genes attributed to mitochondrial respiration. Further analyses of hypoxia-exposed pulmonary artery VSMCs revealed that loss of Nfat5 stimulates the expression of multiple mitochondria-related genes encoding cytochrome oxidases while decreasing the expression of lactate dehydrogenase A (Ldha) and phosphofructokinase 3 (Pfkfb3). Both, inhibition of LDHA or PFKFB3 activity and loss of Nfat5 stimulated the mitochondrial production of reactive oxygen species (ROS) in hypoxic pulmonary artery VSMCs while scavenging of ROS normalized the RVSP values in hypoxia-exposed Nfat5(SMC-/-) mice. In summary, our findings suggest a crucial role for NFAT5 in adjusting the transcriptome of hypoxia-exposed pulmonary artery VSMCs to support an adequate glycolysis-centered metabolism. Loss of Nfat5 impairs this response thereby fueling the mitochondrial respiration and ROS production that amplifies the hypoxia-mediated constriction of pulmonary arteries.
2021-11-26 | GSE178462 | GEO
Project description:Chronic hypoxia causes detrimental structural alterations in the lung, which are partially dependent on stress responses of the endothelium. In this context, we revealed that hypoxia-exposed murine lung endothelial cells (MLEC) activate nuclear factor of activated T-cells 5 (NFAT5/TonEBP) - a transcription factor that adjusts the cellular transcriptome to cope with multiple environmental stressors. Here, we studied the impact of NFAT5 on hypoxia-induced gene expression in MLEC by comparing the transcriptome of control and Nfat5-deficient MLEC, which were isolated from mouse lungs after exposure to normoxia and hypoxia for 7 days and processed for scRNA seq.
2024-08-08 | GSE255681 | GEO
Project description:Hypoxia provokes adaptive responses of cells, which ensure their energy supply including the adjustment of the transcriptome to match their metabolism. In this context, we explored the transcriptional impact of nuclear factor of activated T-cells 5 (NFAT5) on the function of vascular smooth muscle cells (VSMC) in the hypoxic lung. Exposure to hypoxia induced a rapid nuclear translocation of NFAT5 in cultured murine VSMCs. SMC-specific ablation of Nfat5 (Nfat5(SMC-/-)) increases the systolic pressure in the right ventricle (RVSP) of the mouse heart and impairs its function upon exposure to hypoxia for 7 and 21 days. Analyses of the transcriptome of the lung revealed a robust increase in the expression genes attributed to mitochondrial respiration. Further analyses of hypoxia-exposed pulmonary artery VSMCs revealed that loss of Nfat5 stimulates the expression of multiple mitochondria-related genes encoding cytochrome oxidases while decreasing the expression of lactate dehydrogenase A (Ldha) and phosphofructokinase 3 (Pfkfb3). Both, inhibition of LDHA or PFKFB3 activity and loss of Nfat5 stimulated the mitochondrial production of reactive oxygen species (ROS) in hypoxic pulmonary artery VSMCs while scavenging of ROS normalized the RVSP values in hypoxia-exposed Nfat5(SMC-/-) mice. In summary, our findings suggest a crucial role for NFAT5 in adjusting the transcriptome of hypoxia-exposed pulmonary artery VSMCs to support an adequate glycolysis-centered metabolism. Loss of Nfat5 impairs this response thereby fueling the mitochondrial respiration and ROS production that amplifies the hypoxia-mediated constriction of pulmonary arteries.
2021-11-26 | GSE178463 | GEO
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation. Quadruplicate samples were collected for each condition and then pooled into a single sample for hybridization to microarrays.
2010-12-10 | E-GEOD-25816 | biostudies-arrayexpress
Project description:Chronic hypoxic stress stimulates lung endothelial cells to promote vascular remodeling processes, which - in the long run - increase the resistance of pulmonary arteries. While several molecular determinants promoting these maladaptive changes have been delineated, their transcriptional regulation is not well studied. In this context, we revealed that hypoxia activates nuclear factor of activated T-cells 5 (NFAT5/TonEBP) in murine lung endothelial cells (MLECs) - a transcription factor that regulates the adjustment of the cellular transcriptome to cope with osmotic, biomechanical or metabolic environmental stressors. Here, we studied the functional relevance of NFAT5 for the control of endothelial hypoxic stress responses in the lung. Genetic ablation of Nfat5 in endothelial cells did not evoke any obvious phenotypic alterations under normoxia. However, microarray-based transcriptome analyses of lung tissue revealed significant alterations 7 but not 21 days after exposure to normobaric hypoxia (10% O2).
2024-08-08 | GSE230053 | GEO
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
2010-12-10 | GSE25816 | GEO
Project description:Tonicity-Responsive Enhancer-Binding Protein (NFAT5), also known as Tonicity-Responsive Enhancer Binding Protein (TonEBP), is a important transcription factor in the regulation of osmoprotective and inflammatory genes. NFAT5 has been reported to regulate the pathological processes of inflammatory and autoimmune disorders. Our data provides a insight to the gene expression in NFAT5 deficiency BV2 microglia cells, which NFAT5 knocked down by sh-RNA.
2024-02-15 | GSE249968 | GEO
Project description:Chronic hypoxic stress stimulates lung endothelial cells to promote vascular remodeling processes, which - in the long run - increase the resistance of pulmonary arteries. While several molecular determinants promoting these maladaptive changes have been delineated, their transcriptional regulation is not well studied. In this context, we revealed that hypoxia activates nuclear factor of activated T-cells 5 (NFAT5/TonEBP) in murine lung endothelial cells (MLECs) - a transcription factor that regulates the adjustment of the cellular transcriptome to cope with osmotic, biomechanical or metabolic environmental stressors. Here, we studied the functional relevance of NFAT5 for the control of endothelial hypoxic stress responses in the lung. Genetic ablation of Nfat5 in endothelial cells did not evoke any obvious phenotypic alterations under normoxia. However, microarray-based transcriptome analyses of lung tissue revealed significant alterations 7 but not 21 days after exposure to normobaric hypoxia (10% O2).
2024-08-08 | GSE230052 | GEO