Dehydration promotes intracellular lipid synthesis and lipid accumulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE302740 | GEO | 2026/04/10
REPOSITORIES: GEO
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Project description:The corticomedullary osmotic gradient between renal cortex and medulla induces a specific spatial gene expression pattern. The factors that control these differences are not fully addressed. The hypertonic environment leads to activation of the nuclear factor of activated T-cells 5 (NFAT5), which regulates the expression of osmoprotective genes. While NFAT5 function under hypertonic conditions has been extensively studied, its contribution to basal gene 28 regulation remains incompletely understood. We used murine principal kidney cortical collecting duct (mpkCCD) cells and induced functional deletion of NFAT5 and performed gene expression profiling to identify genes that are differentially expressed under isotonic and hypertonic cell culture conditions. Hypertonic stress induced extensive transcriptional changes in control cells, which were markedly altered in NFAT5-deficient cells. Furthermore, the comparison of the mpkCCD transcriptomes with gene expression profiles from renal cortex and inner medulla of control and principal cell-specific NFAT5 knockout mice revealed partial overlap in hypertonicity-associated and NFAT5-dependent gene expression patterns. In both conditions, the expression of known NFAT5 target genes, like Aqp2 or Ranbp3l, was downregulated. These findings support the use of mpkCCD cells as a complementary model to study NFAT5-associated gene regulation under controlled in vitro conditions.
2026-06-25 | GSE326713 | GEO
Project description:Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to osmotic gradient that is generated between renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.3-Cre and Aqp2-Cre) to generate tubule segment and even cell type specific NFAT5 deficient mice in the principal cells of the collecting duct (CD) and in the distal nephron starting in the TAL up to the CD and performed extensive gene expression profiling. In both Nfat5 knockout models, we observed massive changes in gene expression pattern, with heightened inflammatory responses and renal injury, culminating in renal fibrosis. Interestingly, inflammatory responses and fibrosis were much more prominent in the Aqp2Cre+/-Nfat5fl/fl mice that lack NFAT5 only in the collecting duct. By analyzing gene expression in the medullary and cortical regions of the kidney separately, we confirmed that the loss of NFAT5 results in kidney injury that extends beyond hypertonic areas. The correlation between the levels of inflammatory response, injury severity, and fibrosis indicates that cytokines are key mediators of stress signals in the kidney. Thus, NFAT5 is essential not only for adapting to osmotic stress but also for regulating cytokine signaling.
2025-02-05 | GSE276474 | GEO
Project description:Hypertonicity in renal medulla is essential for urine concentration and water homeostasis. However, how renal medullary collecting duct cells (MCDs) survive and function under the harsh hypertonic stress remains incompletely understood. By using the RNA-seq technique, we identified SNAT2 (slc38a2) as a novel osmoresponsive neutral amino acid transporter in MCD cells. We found that hypertonic stress induced cell death of MCDs mainly via ferroptosis.
2023-02-15 | GSE206476 | GEO
Project description:Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense and enable adaptation to ionic stress remain poorly understood in animals. We find that the transcription factor NFAT5 directly senses solution ionic strength using a C-terminal intrinsically disordered region. Both in intact cells and in a purified system, NFAT5 forms dynamic, reversible biomolecular condensates in response to increasing ionic strength. This self-associative property, conserved from insects to mammals, allows NFAT5 to accumulate in the nucleus and activate genes that restore cellular ion content. Mutations that reduce condensation or those that promote aggregation both reduce NFAT5 activity, highlighting the importance of optimally tuned associative interactions. To investigate the composition of NFAT5 condensates in response to hypertonic stress, proteins in close proximity of NFAT5 were identified using a variant of NFAT5 fused to TurboID as bait. Hypertonic stress increases NFAT5 proximity to protein complexes belonging to the GO gene sets of “transcription coactivator activity” and “positive regulation of DNA templated transcription initiation.” Closer inspection revealed that the association between NFAT5 and two transcriptional co-activators (the mediator complex and BRD4) and RNAPII itself increased in response to hypertonic stress.
2025-04-17 | PXD052591 | Pride
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:Transcriptional profile of inner medullary collecting duct cells in response to overnight NaCl hypertonic stress
2025-08-08 | GSE274371 | GEO
Project description:Osmotic stress represents a major challenge to cells, particularly in the kidney, where tonicity gradients are both physiologically relevant and pathologically altered. The transcription factor NFAT5 is a key regulator of the osmoadaptive response, yet its downstream metabolic effectors remain incompletely understood.
2026-03-11 | GSE308904 | GEO
Project description:Response of collecting duct cells to hypertonic stress
| PRJNA1146070 | ENA
Project description:Immune cells regulate a hypertonic microenvironment in the skin; however, possible functions of increased skin Na+ concentrations are unknown. We found that Na+ accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania (L.) major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na+ storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved L. major elimination. Finally, we found that increasing Na+ content in the skin by a high-salt diet boosted activation of macrophages in an Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.
2015-02-26 | E-MTAB-3343 | biostudies-arrayexpress
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