Effect of NFAT5 deficiency on gene expression in BV2 cells
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ABSTRACT:
PROVIDER: PRJNA1051522 | ENA |
REPOSITORIES: ENA
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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.
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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.
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