Transcriptomes regulated by NFAT5 in RAW264.7 macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE76554 | GEO | 2017/01/05
SECONDARY ACCESSION(S): PRJNA307705
REPOSITORIES: GEO
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2018-09-26 | GSE107948 | GEO
Project description:Chromatin from wild-type and NFAT5-deficient BMDM was immunoprecipitated with anti-NFAT5 antibodies and ultrasequenced to identify NFAT5 binding sites in steady state macrophages (BMDM)
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Project description:NFAT5 is an osmoprotective transcription factor whose DNA binding domain shares structural homology with NFkappaB and other member of NFAT family, but its role in chronic inflammatory diseases remains unclear. The mRNA profiling of synoviocytes and endothelial cells transfected with NFAT5-targeted siRNA reveals three major changes in cellular processes associated with the pathogenesis of rheumatoid arthritis: cell cycle and survival, angiogenesis, and cell migration. The cells were transfected with NFAT5-targeted siRNA or non-specific scrambled (control) siRNA.
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Project description:The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most frequent epidermal cells, and it is anticipated that KC-mediated transport of Na+ ions creates a physiological barrier of high osmolality against the external environment. We studied in KCs the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress. Cultured KCs from adult mice secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of Nfat5-/- KCs, along with increases of numerous components of ‘Epidermal Differentiation Complex’ (EDC), as proline-rich Sprr and S100 proteins. NFAT5 and Mmp3 are co-expressed in basal KCs from fetal and adult skin but not in skin of newborn mice. This is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of newborn mice and suggests, along with the fragile epidermis of adult Nfat5-/- mice, a suppressive effect of NFAT5 on the expression of matrix proteases in skin. Our data suggest that NFAT5 controls the expression of matrix proteases in skin and contributes to the many fold changes during embryonal skin development and skin integrity in adults.
2021-11-16 | PXD028675 | Pride
Project description:Endothelial cell-specific genetic ablation of Nfat5 was induced in adult mice. These anmials and control mice were exposed to hypoxia (10% oxygen) for 7 days. The lungs were processed for RNA exptraction and further analyses of the transcriptome
2021-11-26 | GSE178461 | GEO
Project description:Purpose: To investigate the involvement of Nfat5 in the regulation of an ibuprofen transporter Method: Reverse transfection with siRNA against Nfat5 was used to knockdown Nfat5 in MDCK I cells. The uptake of both radiolabelled taurine and ibuprofen was measured in MDCK I cells, first treated with siRNA against Nfat5 for 24 h and afterwards cultivated with raffinose-supplemented normal growth medium (500 mOsm) for 24 h. The knock down of NFat5 was investigated by qpCR and western blotting. A transcriptome analysis of MDCK I cells treated with siRNA against Nfat5 was performed. Validation of the transcriptome analysis was perform with qPCR and radiolabelled uptake of ibuprofen. Results: The siRNA transfection resulted in a knock down of Nfat5, and the uptake of both taurine and ibuprofen was significant decreased in the transfected MDCK I cells. The transcriptome analysis of MDCK I cells treated with siRNA against Nfat5 revealed genes regulated by Nfat5 during hyperosmotic exposure. qPCR and the transciptome analysis showed an involvement of Nfat5 in the hyperosmotic regulation of Tmem184 and uptake in Tmem184b-siRNA treated MDCK I cells showed that Tmem184b might be involved in uptake of ibuprofen. Conclusion: The regulation of Tmem184b was found regulated by Nfat5 and could be a potential possible candidate for the gene product responsible for the uptake of ibuprofen in MDCK I cells
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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.
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Project description:The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most frequent epidermal cells, and it is anticipated that KC-mediated transport of Na+ ions creates a physiological barrier of high osmolality against the external environment. We studied in KCs the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress. Cultured KCs from adult mice secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of Nfat5-/- KCs, along with increases of numerous components of ‘Epidermal Differentiation Complex’ (EDC), as proline-rich Sprr and S100 proteins. NFAT5 and Mmp3 are co-expressed in basal KCs from fetal and adult skin but not in skin of newborn mice. This is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of newborn mice and suggests, along with the fragile epidermis of adult Nfat5-/- mice, a suppressive effect of NFAT5 on the expression of matrix proteases in skin. Our data suggest that NFAT5 controls the expression of matrix proteases in skin and contributes to the many fold changes during embryonal skin development and skin integrity in adults.
2021-12-29 | GSE184178 | GEO
Project description:The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most frequent epidermal cells, and it is anticipated that KC-mediated transport of Na+ ions creates a physiological barrier of high osmolality against the external environment. We studied in KCs the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress. Cultured KCs from adult mice secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of Nfat5-/- KCs, along with increases of numerous components of ‘Epidermal Differentiation Complex’ (EDC), as proline-rich Sprr and S100 proteins. NFAT5 and Mmp3 are co-expressed in basal KCs from fetal and adult skin but not in skin of newborn mice. This is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of newborn mice and suggests, along with the fragile epidermis of adult Nfat5-/- mice, a suppressive effect of NFAT5 on the expression of matrix proteases in skin. Our data suggest that NFAT5 controls the expression of matrix proteases in skin and contributes to the many fold changes during embryonal skin development and skin integrity in adults.
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