Kidney gene expression in response to high phosphate diet
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE223176 | GEO | 2023/03/20
REPOSITORIES: GEO
Similar Datasets
Project description:Although disturbed phosphate metabolism frequently accompanies chronic kidney disease, it is unclear whether it contributes to the progression of renal dysfunction. Here, we show that urinary phosphate-containing nanoparticles promote kidney injury in salt-sensitive hypertension. Remarkably, four weeks of high salt loading resulted in a 2.5-fold increase in urinary phosphate excretion in Dahl salt-sensitive rats on a normal phosphorus diet. Inhibition of intestinal phosphate absorption using sucroferric oxyhydroxide (SF) in this model suppressed phosphaturia, attenuating glomerulosclerosis and tubulointerstitial injury without significantly affecting serum phosphate, blood pressure, or urinary sodium levels. In the kidney, macrophage infiltration and inflammatory cytokine induction were ameliorated by SF. Additionally, macrophage infiltration but not myofibril hypertrophy was alleviated in the heart. In vitro, phosphate loading to proximal tubule cells significantly increased inflammatory cytokine Ccl2, which was abolished by the removal of phosphate-containing nanoparticles but not by the knockdown of phosphate transporter Slc34a1. Finally, transcriptome analysis revealed a potential role of complement C1q in renal inflammation associated with disturbed phosphate metabolism. These data demonstrate that increased phosphaturia promotes inflammation and renal injury from an early stage of salt-sensitive hypertension, and suggest the need for interventions against subclinical phosphate accumulation to improve the prognosis of hypertensive kidney disease.
2020-08-22 | GSE143440 | GEO
Project description:The renal adaptation to changing dietary phosphate levels is not well understood. The dominant Hyp mutation of the Phex gene in mice causes X-linked hypophosphatemia with low renal retention of phosphate and blocks physiologic adaptation to low phosphate diets. At P < 0.01, there were 1,711 transcripts significantly affected by genotype, 1,428 by diet and 5,601 by sex. Many renal transporters other than phosphate, as well as many novel transcripts of unknown function, were affected by the Hyp mutation. Some genes for fat metabolism and inflammation were up-regulated in Hyp kidneys. Of the genes affected by genotype and diet, only 378 were affected by both. In summary, the Hyp mutation induced changes in mRNA levels for numerous transcripts exceeding that required to alter phosphate retention. The data suggest broader physiological roles for the Phex gene unrelated to phosphate conservation. Keyword = Phex; Keyword = Hyp; Keyword = mouse; Keyword = kidney; Keyword = sex; Keyword = mRNA; Keyword = microarray; Keyword = low phosphorus diet Experiment Overall Design: A 2x2x2 factorial design, balanced for genotype (normal vs. Hyp), diet (control vs. low phosphate), and sex (male vs. female) was employed. Control or low phosphate diets were fed for three days to 10-week-old mice. A total of 24 samples of renal RNA were collected from 72 mice (3/array), processed to biotin-labeled cRNA, and hybridized to Affymetrix mouse MOE 430A and 430B for measurement of expression of over 45,000 transcripts.
2008-06-13 | E-GEOD-5243 | biostudies-arrayexpress
Project description:The renal adaptation to changing dietary phosphate levels is not well understood. The dominant Hyp mutation of the Phex gene in mice causes X-linked hypophosphatemia with low renal retention of phosphate and blocks physiologic adaptation to low phosphate diets. At P < 0.01, there were 1,711 transcripts significantly affected by genotype, 1,428 by diet and 5,601 by sex. Many renal transporters other than phosphate, as well as many novel transcripts of unknown function, were affected by the Hyp mutation. Some genes for fat metabolism and inflammation were up-regulated in Hyp kidneys. Of the genes affected by genotype and diet, only 378 were affected by both. In summary, the Hyp mutation induced changes in mRNA levels for numerous transcripts exceeding that required to alter phosphate retention. The data suggest broader physiological roles for the Phex gene unrelated to phosphate conservation. Keyword = Phex Keyword = Hyp Keyword = mouse Keyword = kidney Keyword = sex Keyword = mRNA Keyword = microarray Keyword = low phosphorus diet Keywords: disease state analysis
2007-01-01 | GSE5243 | GEO
Project description:Transcriptional profiling related cytokines and chemokines of mouse kidneys comparing the kidneys of WNK4 D561A/+ mice fed an 8% high-salt diet with those of WNK4+/+ littermates with a normal diet. Goal was to determine the effects of a high-salt condition on the immune system in kidney.
2017-06-12 | GSE87600 | GEO
Project description:Hyperphosphatemia is an independent risk factor for cardiovascular mortality in chronic kidney disease. High inorganic phosphorus can induce endothelial cell apoptosis, but the exact mechanism is not fully understood. This study addresses this knowledge gap.Microarray analysis was used to identify differentially expressed gene profiles in human umbilical vein endothelial cells (HUVECs) in high phosphate (3.0 mM) normal phosphate (1.0 mM) medium and low phosphate( 0.5mM).
2014-08-30 | GSE60937 | GEO
Project description:This is a study of the change in gene expression in mouse kidney after feeding control (1.0% P) or low phosphate diet (0.03% P) for 3 or 5 days to normal or Hyp (X-linked hypophosphatemic) mice at 5 weeks of age. The mice were C57BL/6J. Normal wild-type mice, hemizygous Hyp (Hyp/Y) male mice, or heterozygous (Hyp/+) female mice were used. The gene is dominant, so that the two genders are equally affected with low renal retention of phosphate and severity of their bone disease. RNA from 3 mice were pooled for each microarray. The arrays were processed as described in the Affymetrix GeneChip Expression Analysis Technical Manual (copyright 2001, Affymetrix, Inc., Santa Clara, CA), rev. 1, Part number 701021. The data for each array were scaled to an average signal value of 500 for all genes on the array. Keywords = mouse Keywords = kidney Keywords = low phosphate diet Keywords = Hyp Keywords = Phex Keywords = X-linked hypophosphatemia Keywords: repeat sample
2004-05-10 | GSE868 | GEO
Project description:Hyperphosphatemia is an independent risk factor for cardiovascular mortality in chronic kidney disease. High inorganic phosphorus can induce endothelial cell apoptosis, but the exact mechanism is not fully understood. This study addresses this knowledge gap.Microarray analysis was used to identify differentially expressed gene profiles in human umbilical vein endothelial cells (HUVECs) in high phosphate (3.0 mM) normal phosphate (1.0 mM) medium and low phosphate( 0.5mM). Differential gene expression in HUVECs seeded in high phosphate (3.0 mM ) medium ,normal phosphate ( 1.0 mM ) medium and simulated hypophosphatemia (0.5mM) were identified using Affymetrix GeneChip Human Gene 1.0 ST arrays ( Affymetrix ). Three chips were used to minimize the random error in each group.
2014-08-30 | E-GEOD-60937 | biostudies-arrayexpress
Project description:FGF23 is a bone-derived hormone that mediates renal phosphate reabsorption and 1,25(OH)2 vitamin D metabolism via its required co-receptor alpha-Klotho (KL). The functional pathways guiding this hormone’s activity in kidney have not been studied extensively, and whether using other factors with overlapping signaling profiles to produce FGF23-like responses is unclear. To map FGF23-related genes, gene array and single-cell RNA sequencing were utilized on wild type mouse kidneys. After identifying Heparin-binding EGF-like growth factor (HBEGF) as an up-regulated gene in response to FGF23 delivery, KL-null and phosphate-deficient diet fed mouse models and in vitro experiments were utilized to further test HBEGF bioactivity in kidney. Gene array demonstrated that HBEGF was significantly up-regulated following FGF23 delivery to wild type (WT) mice. Next, mice injected with HBEGF had phenotypes consistent with partial FGF23-mimetic activity including robust induction of EGR1, and increased CYP24A1 mRNAs. Single cell RNA sequencing showed overlapping HBEGF and EGFR expression in the proximal tubule (PT), and KL expression in PT and distal tubule (DT) segments. In KL-null mice devoid of canonical FGF23 signaling, HBEGF injections significantly increased EGR1 and CYP24A, and correction of basally-elevated CYP27B1 was observed. In addition, mice placed on a phosphate deficient diet to suppress FGF23 had endogenously increased CYP27B1 mRNA, which was rescued in mice receiving HBEGF. In HEK293 renal epithelial cells, HBEGF and FGF23 increased CYP24A1 mRNA. Targeting pathways known to be downstream of FGF23 in kidney may help to control renal phosphate handling in diseases of altered FGF23 bioactivity.
2020-10-01 | GSE138992 | GEO
Project description:This is a study of the change in gene expression in mouse kidney after feeding control (1.0% P) or low phosphate diet (0.03% P) for 3 or 5 days to normal or Hyp (X-linked hypophosphatemic) mice at 5 weeks of age. The mice were C57BL/6J. Normal wild-type mice, hemizygous Hyp (Hyp/Y) male mice, or heterozygous (Hyp/+) female mice were used. The gene is dominant, so that the two genders are equally affected with low renal retention of phosphate and severity of their bone disease. RNA from 3 mice were pooled for each microarray. The arrays were processed as described in the Affymetrix GeneChip Expression Analysis Technical Manual (copyright 2001, Affymetrix, Inc., Santa Clara, CA), rev. 1, Part number 701021. The data for each array were scaled to an average signal value of 500 for all genes on the array.
2007-12-13 | E-GEOD-868 | biostudies-arrayexpress
Project description:Global gene expression in the 20-week remnant kidneys of uninephrectomized mice fed either a chow or a high fat diet was compared with kidney tissue from the corresponding sham groups. Results provide insight into mechanisms underlying effects of high-fat induced obesity on gene expression in mouse kidney. Male C57/BJ mice aged 6 weeks were randomly assigned to uninephrectomy (UNX) or sham procedures and fed with a high fat diet or control chow diet. All mice were sacrificed under anesthesia 20 weeks after surgery and kidneys were harvested. 3-4 total RNA samples per group were analyzed and gene expression was compared between groups.
2014-01-11 | E-GEOD-53996 | biostudies-arrayexpress