Similar Datasets
Project description:To compare the transcriptional profile in aged kidneys lacking tubular Cpt1a with floxed littermate controls.
2024-03-01 | GSE205497 | GEO
Project description:Circadian variability in kidney function has long been recognized but is often ignored as a potential confounding variable in in vivo physiological experiments. To provide a guide for physiological studies on the kidney proximal tubule, we have now created a data resource consisting of expression levels for all measurable mRNA transcripts in microdissected proximal tubule segments from mice as a function of the time of day. This approach employs small-sample RNA-sequencing (RNA-seq) applied to microdissected renal proximal tubules including both S1 proximal convoluted tubules (PCTs) and S2 proximal straight tubules (PSTs). The data were analyzed using JTK-Cycle to detect periodicity. The data are provided as a user-friendly web page at https://esbl.nhlbi.nih.gov/Databases/Circadian-Prox/. In PCTs, 234 transcripts were found to vary in a circadian manner (3.7 % of total quantified). In PSTs, 334 transcripts were found to vary in a circadian manner (5.3 % of total quantified). Transcripts previously known to be associated with corticosteroid action and transcripts associated with increased flow were found to be overrepresented among circadian transcripts peaking during the “dark” portion of the day (Zeitgeber 14-22), corresponding to the peak levels of corticosterone and glomerular filtration rate in mice.
2023-04-10 | PXD039006 | Pride
Project description:Peroxisomes are highly abundant in proximal tubules where peroxisomal enzymes have been proposed to play an important role in a variety of metabolic and antioxidant functions. This hypothesis was supported by human genetic studies that identified mutations leading to peroxisomal biogenesis deficiency, resulting in severe multi-organ damage (Zellweger’s spectrum disorders (ZSD)), including renal impairment. However, the role of proximal tubule peroxisomes in renal (patho)physiology remains uninvestigated. We addressed this question in mice with conditional ablation of peroxisomal biogenesis in the renal tubule. Our results demonstrate that renal tubular peroxisomes are dispensable for normal renal function and suggest that renal damage in ZSD patients is of extrarenal origin.
2022-03-02 | GSE179202 | GEO
Project description:Acute kidney injury (AKI) have been thought to be reversible condition, however, emerging evidence demonstrated association between AKI and subsequent development of irreversible fibrosis and chronic kidney disease. In the present study, since recovery of AKI depends on renal tubular regeneration, factors expressing in renal tubules in adaptive or maladaptive repair process were investigated to predict reversibility of kidney injury. In the kidney of female F344 rats subjected to ischemia/reperfusion (I/R), regenerative tubules and dilated tubules were observed at 3 and 7 days after I/R. In fibrotic areas of the kidney of male SD rats subjected to I/R, renal tubules were dilated or atrophied. From microarray data of regenerative tubules, survivin, sex-determining region Y (SRY)-box 9 (SOX9), and CD44 were extracted as factors possibly relating to tubular regeneration or fibrosis. Immunohistochmical analysis demonstrated that survivin and SOX9 expressed in regenerative tubules, while SOX9 also expressed in renal tubules in fibrotic area, indicating that survivin and SOX9 contribute renal tubular regeneration, but sustained SOX9 expression may lead fibrosis. CD44 expressed in dilated tubules at day 3 and 7, and tubules in fibrotic area, suggesting that CD44 expressed in maladaptive tubules. These information will be helpful to consider reversibility of kidney injury.
2020-06-01 | GSE148420 | GEO
Project description:To clarify the effects of cisplatin (cis-diamminedichloroplatinum II, CDDP) on the gene expression profiles in renal proximal tubules, microarray analyses were carried out using total RNA samples isolated from microdissected proximal tubules and whole kidneys. The molecular events underlying acute kidney injury (AKI) in the proximal tubules of rats with cisplatin-induced nephrotoxicity were successfully clarified with 17,000 transcripts. Renal proximal tubules were isolated under microscopy, and transcriptome data were collected with Rat Genome Survey Microarray® (Applied Biosystems)
2013-12-24 | E-GEOD-37133 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in kidney fibrosis and contributes to its pathogenesis. To determine whether gain of function in FAO (FAO-GOF) could protect from fibrosis, we generated a conditional transgenic mouse model with overexpression of the fatty acid shuttling enzyme carnitine palmitoyl-transferase 1A (CPT1A) in TECs. Cpt1a-knockin (CPT1A-KI) mice subjected to 3 models of renal fibrosis (unilateral ureteral obstruction, folic acid nephropathy [FAN], and adenine-induced nephrotoxicity) exhibited decreased expression of fibrotic markers, a blunted proinflammatory response, and reduced epithelial cell damage and macrophage influx. Protection from fibrosis was also observed when Cpt1a overexpression was induced after FAN. FAO-GOF restored oxidative metabolism and mitochondrial number and enhanced bioenergetics, increasing palmitate oxidation and ATP levels, changes that were also recapitulated in TECs exposed to profibrotic stimuli. Studies in patients showed decreased CPT1 levels and increased accumulation of short- and middle-chain acylcarnitines, reflecting impaired FAO in human CKD. We propose that strategies based on FAO-GOF may constitute powerful alternatives to combat fibrosis inherent to CKD.
| S-EPMC7919728 | biostudies-literature
Project description:Multipotent progenitor cells (MPs) have been observed in human kidneys and particularly in Bowman's capsule and proximal tubules. The kidney owns the ability to repair local damage and renal MPs may play a role in the regenerative processes. Microarray technology was applied to identify differentially expressed genes among resident MPs isolated from glomeruli and tubules of normal renal tissue, renal proximal tubular epithelial cells (RPTECs) and mesenchymal stem cells (MSCs). The results of our analysis represent a starting point for further functional studies. Keywords: cell type comparison
2009-11-03 | GSE8611 | GEO
Project description:Different segments of renal tubules have distinct metabolic features and functions, and defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined. We demonstrated that the renal proximal tubule (PT) has high expression of fatty acid and lipid metabolism enzymes, which is transcriptionally upregulated by abundantly expressed peroxisome proliferator-activated receptor (PPAR)/γ to support active lipid metabolism. In contrast, the renal distal tubule (DT) has elevated glycolytic enzyme expression corresponding with high rates of glycolysis, and this increased expression is mediated by abundantly expressed c-Myc. In addition, Nrf2 upregulated glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-dependent malic enzyme 1 expression for NADPH production and antioxidation in the DT. Highly expressed PPARγ transcriptionally enhanced expression of the protease iRhom2 in the PT, which suppressed epidermal growth factor (EGF) expression and secretion, inhibiting EGF receptor activation-dependent glycolytic gene expression and maintaining the low level of glycolysis. PPARγ inhibition reduced iRhom2 expression and increased EGF and GLUT1 expression in the PT in mice, resulting in hypertrophy of renal tubules and inhibited kidney functions, which can be rescued by inhibition of glycolysis via treatment with 2-deoxy-D-glucose. These findings delineate instrumental molecular mechanisms underlying the active lipid metabolism and suppressed glycolysis in the PT and active glycolysis in the DT and reveal critical roles for PPARs and c-Myc in maintaining metabolic homeostasis in the kidney
2018-11-15 | PXD007828 | Pride
Project description:To clarify the effects of cisplatin (cis-diamminedichloroplatinum II, CDDP) on the gene expression profiles in renal proximal tubules, microarray analyses were carried out using total RNA samples isolated from microdissected proximal tubules and whole kidneys. The molecular events underlying acute kidney injury (AKI) in the proximal tubules of rats with cisplatin-induced nephrotoxicity were successfully clarified with 17,000 transcripts.
2013-12-24 | GSE37133 | GEO
Project description:Introduction: There is evidence that patients with a history of ileostomies, who produce acidic urine and form uric acid or calcium oxalate stones, may plug some collecting ducts with calcium phosphate (CaP) and urate crystals. This is a paradoxical finding as such minerals should not form at an acid pH. One possible explanation is the presence of acidification defects due to focal damage to inner medullary collecting duct and Bellini duct (BD) cells. We sought to further investigate this hypothesis through direct measurement of ductal pH in dilated BDs in patients with ileostomies undergoing percutaneous nephrolithotomy (PCNL) for stone removal. Methods: After obtaining institutional review board approval, we used a fiber-optic pH microsensor with a 140-?m-diameter tip to measure intraluminal pH from the bladder, saline irrigant, and dilated BDs of patients undergoing PCNL. Results: Measurements were taken from three patients meeting inclusion criteria. Measured pH of bladder urine ranged from 4.97 to 5.58 and pH of saline irrigant used during surgery ranged from 5.17 to 5.75. BD measurements were achieved in 11 different BDs. Mean intraductal BD pH was more than 1 unit higher than bulk urine (6.43?±?0.22 vs 5.31?±?0.22, p?<?0.01). Conclusions: This is the first evidence for focal acidification defects within injured/dilated BDs of human kidneys producing highly acidic bulk phase urine. These results may help explain the paradoxical finding of CaP and urate plugs in dilated ducts of patients with stone-forming diseases characterized by highly acidic urine.
| S-EPMC7047079 | biostudies-literature