High NaCl activates the transcription factor nuclear factor of activated T cells 5 (NFAT5), leading to increased transcription of osmoprotective target genes. Kinases PKA, PI3K, AKT1, and p38α were known to contribute to the high NaCl-induced increase of NFAT5 activity. We now identify another kinase, GSK-3β. siRNA-mediated knock-down of GSK-3β increases NFAT5 transcriptional and transactivatin...

NFAT5 is a transcription factor that protects the kidney from hypertonic stress and also is activated by hypoxia. We hypothesized that NFAT5 mitigates the extent of renal damage induced by ischemia-reperfusion injury (IRI). Mice were subjected to IRI by unilateral clamping of the left renal pedicle for 30 minutes followed by reperfusion. After 3 hours of reperfusion, the level of NFAT5 mRNA was...

26 27 The effects of Na-K-2Cl cotransporter type 2 (NKCC2) isoforms on the regulation of nuclear 28 factor of activated T cells isoform 5 (NFAT5) was determined in mouse medullary thick ascending 29 limb (mTAL) cells exposed to high NaCl concentration. Primary cultures of mTAL cells and freshly 30 isolated mTAL tubules, both derived from outer medulla (outer stripe>inner stripe), express NKCC2 ...

Nuclear factor of activated T-cells 5 (NFAT5) is a well-known osmoprotective transcription factor the amount and nuclear distribution of which is increased in a hyperosmolaric environment. Recently, NFAT5 was shown to control the phenotype of vascular smooth muscle cells (VSMCs) in the context of arteriosclerosis and neointimal hyperplasia by regulating the expression of smooth muscle cell diff...

The osmosensitive transcription factor nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity enhancer element binding protein (TonEBP) plays a crucial role in protection of renal medullary cells against hyperosmotic stress, urinary concentration, the adaptive immune response, and other physiological systems. Since it is also important for development, conventional homozygous-nul...

Breast cancer is a complex genetic disease that has an average annual incidence of two million people and the second leading cause of death among women all over the world. Micro-RNAs are consistently reported to regulate gene expression in all cancers. The present study, the correlation between the expression of hsa-miR-490-5p and nuclear factor of activated T-cells 5 (NFAT5) in breast cancer w...

The osmosensitive transcription factor nuclear factor of activated T-cells (NFAT) 5, also known as tonicity enhancer binding protein (TonEBP), has been associated with the development of a variety of tumor entities, among them breast cancer, colon carcinoma, and melanoma. The aim of the present study was to determine whether NFAT5 is also involved in the development of renal cell carcinoma (RCC...

The localization and regulation of (pro)renin receptor (PRR) expression in kidney collecting duct cells are not well established. We hypothesized that low salt (LS) contributes to the regulation of PRR expression in these cells via the GSK-3β-NFAT5-sirtuin1 (SIRT-1) signaling pathway. Mouse inner medullary collecting duct (mIMCD) cells were treated with NaCl at 130 (normal salt; NS), 63 (LS), o...

The transcription factor NFAT5/TonEBP, a member of the NFAT/Rel family of transcription factors, has been implicated in diverse cellular responses, including the response to osmotic stress, integrin-dependent cell migration, T cell activation, and the Ras pathway in Drosophila. To clarify the in vivo role of NFAT5, we generated NFAT5-null mice. Homozygous mutants were genetically underrepresent...

High NaCl in the renal medullary interstitial fluid powers the concentration of urine but can damage cells. The transcription factor nuclear factor of activated T cells 5 (NFAT5) activates the expression of osmoprotective genes. We studied whether PKC-α contributes to the activation of NFAT5. PKC-α protein abundance was greater in the renal medulla than in the cortex. Knockout of PKC-α reduced ...