Gene expression analysis of human mortal renal tubular epithelial cells chronically exposed to elevated levels of glucose
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168072 | GEO | 2021/03/07
REPOSITORIES: GEO
Similar Datasets
Project description:Tight control of both extracellular and intracellular inorganic phosphate (Pi) levels is critical to the normal functioning of virtually all biochemical and physiological processes. The kidney participates in Pi homeostasis by controlling Pi reabsorption from the primary urine. Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium-dependent phosphate transporters NaPi-IIa/NaPi-IIc/Pit2. The molecular identity of transporter(s) involved in the basolateral Pi efflux remains unknown. Recent evidence has suggested that the retroviral receptor XPR1 might be a candidate for this role. Here we show that conditional inactivation of Xpr1 in the renal tubule in mice results in impaired renal Pi reabsorption associated with a generalized proximal tubular dysfunction, or Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria and albuminuria. Bone histomorphometry showed that the Xpr1-deficient mice develop hypophosphatemic osteomalacia secondary to the renal dysfunction. The analysis of Pi transport in primary culture of the proximal tubular cells revealed that the Pi efflux was significantly affected in cells devoid of Xpr1. These results identify XPR1 as a major player in Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.
2016-12-01 | GSE87450 | GEO
Project description:In diabetes, the kidney contributes to the development of diabetic hyperglycemia by increasing glucose reabsorption from the primary urine and by upregulating gluconeogenesis in the proximal tubule. However, these two processes are also controlled by the circadian clock, a mechanism that synchronizes a large number of specific renal functions with environmental daily cycles. Here, we investigated the (patho)physiological role of intrinsic renal tubule circadian clocks in the diabetic kidney. We demonstrate that diabetic mice devoid of the circadian transcriptional regulator BMAL1 in the renal tubule exhibit additional enhancement of renal gluconeogenesis, exacerbated hyperglycemia, increased glucosuria, polyuria and renal hypertrophy. Collectively, our results suggest that diabetic hyperglycemia can be worsened by dysfunction or misalignment of intrinsic renal circadian clocks.
2022-05-27 | GSE178319 | GEO
Project description:Introduction: The kidney is the major arbiter of extracellular phosphate homeostasis. The vast majority of glomerular filtrated phosphate is reabsorbed in the proximal tubule. Posttransplant phosphaturia is common and aggravated by sirolimus immunosuppression. The cause of sirolimus induced phosphaturia however remains elusive. Results: The urine phosphate/creatinine ratio was higher and serum phosphate was lower in sirolimus treated rats, fractional excretion of phosphate was elevated and renal tubular phosphate reabsorption was reduced suggesting a renal cause for hypophosphatemia. PTH was lower in sirolimus treated rats. FGF 23 levels were unchanged at day 2 but lower in sirolimus treated rats after 7 days. Brush border membrane vesicle phosphate uptake was not altered in sirolimus treated groups or by direct incubation with sirolimus. mRNA, protein abundance, and subcellular transporter distribution of NaPi-IIa, Pit-2 and NHE3 were not different between groups but NaPi-IIc mRNA expression was lower at day 7. Transcriptome analyses revealed candidate genes that could be involved in the phosphaturic response. Discussion: Sirolimus caused a selective renal phosphate leakage which was not mediated by NaPi-IIa or NaPi-IIc regulation or localization. We hypothesize that another mechanism such as a basolateral phosphate transporter may be responsible for the sirolimus induced phosphaturia. Male Wistar rats received sirolimus or vehicle for 7 days (1.5mg/kg) and were placed in individual metabolic cages for eight days allowing a 24 hour adaption period to the metabolic cage environment. At the end of the experiments rats were anesthetized by inhalation of Isoflurane/air and blood samples and kidneys were collected. 4 cases (sirolimus) and 4 controls (vehicle) have been analysed
2012-09-24 | E-GEOD-35048 | biostudies-arrayexpress
Project description:Gene expression analysis of human mortal renal tubular epithelial cells chronically exposed to elevated levels of glucose
| PRJNA705982 | ENA
Project description:Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that ~30% RNAs, ~20% proteins and ~20% metabolites are rhythmic in kidneys of control mice. Several key metabolic pathways including NAD+ biosynthesis, fatty acid transport, carnitine shuttle, and b-oxidation displayed impairments in kidneys of cKOt, resulting in a perturbed mitochondrial activity. Carnitine reabsorption from the primary urine was one of the most impacted processes with a ~50% reduction in plasma carnitine levels and a parallel systemic decrease in tissues carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.
2023-03-05 | GSE216252 | GEO
Project description:Poorly defined adaptive processes maintain salt balance when the renal thiazide-sensitive sodium-chloride cotransporter is inhibited, limiting diuretic efficacy. Here, we identify underlying mechanisms in SPAK kinase null mice, which are unable to phospho-activate NCC. Global transcriptional profiling, combined with biochemical, cell biological and physiological phenotyping, identified the gene expression signature of the response, and revealed how it establishes a new adaptive physiology. Salt reabsorption pathways are created by the coordinate induction of a multi-gene transport system, involving solute carriers (Slc26a; Slc4a8; Slc4a9), carbonic anhydrase isoforms, and V-type H+-ATPase subunits in pendrin-positive intercalated cells (PP-IC), and ENaC subunits in principal cells. A distal nephron remodeling process and induction of Jagged 1-Notch signaling, which expands the cortical connecting tubule with principal cells and replaces acid-secreting ?- intercalated cells with PP-IC, is partly responsible. Salt reabsorption is also activated by induction of an alpha-ketoglutarate (?-KG) paracrine signaling system. Coordinate regulation of a multigene ?-KG synthesis and transport pathway cause ?-KG to be secreted into the pro-urine as the ?-KG activated GPCR (Oxgr1) increases on the PP-IC apical surface, allowing paracrine delivery of ?-KG to stimulate salt transport. Identification of the integrated compensatory NaCl reabsorption mechanisms provides new insights into thiazide diuretic efficacy. Gene transcrtipt isolated form the renal cortex of 4 SPAK KO and 4 litter-mate WT animals was compared to evaluate differential gene expression with the goal of identifing a nextwork of genes that function cooperatively compensatory to mitigate renal salt loss when the SPAK function is lost.
2014-11-01 | E-GEOD-60728 | biostudies-arrayexpress
Project description:The experiment was designed to identify genes abundant or enriched in adult Drosophila melanogaster Malpighian (renal) tubule as compared to the whole fly.
2004-06-23 | E-MEXP-127 | biostudies-arrayexpress
Project description:Introduction: The kidney is the major arbiter of extracellular phosphate homeostasis. The vast majority of glomerular filtrated phosphate is reabsorbed in the proximal tubule. Posttransplant phosphaturia is common and aggravated by sirolimus immunosuppression. The cause of sirolimus induced phosphaturia however remains elusive. Results: The urine phosphate/creatinine ratio was higher and serum phosphate was lower in sirolimus treated rats, fractional excretion of phosphate was elevated and renal tubular phosphate reabsorption was reduced suggesting a renal cause for hypophosphatemia. PTH was lower in sirolimus treated rats. FGF 23 levels were unchanged at day 2 but lower in sirolimus treated rats after 7 days. Brush border membrane vesicle phosphate uptake was not altered in sirolimus treated groups or by direct incubation with sirolimus. mRNA, protein abundance, and subcellular transporter distribution of NaPi-IIa, Pit-2 and NHE3 were not different between groups but NaPi-IIc mRNA expression was lower at day 7. Transcriptome analyses revealed candidate genes that could be involved in the phosphaturic response. Discussion: Sirolimus caused a selective renal phosphate leakage which was not mediated by NaPi-IIa or NaPi-IIc regulation or localization. We hypothesize that another mechanism such as a basolateral phosphate transporter may be responsible for the sirolimus induced phosphaturia. Male Wistar rats received sirolimus or vehicle for 7 days (1.5mg/kg) and were placed in individual metabolic cages for eight days allowing a 24 hour adaption period to the metabolic cage environment. At the end of the experiments rats were anesthetized by inhalation of Isoflurane/air and blood samples and kidneys were collected.
2012-09-24 | GSE35048 | GEO
Project description:Drugs and other xenobiotics are not only secreted/reabsorbed by the renal proximal tubule epithelial cells (RPTEC) but may also adversely impact kidney function. In vitro models that can afford prediction of toxic effects and model directional transport are in high demand in both drug and chemical safety; accordingly, active development of new models is underway. The objective of this study was to investigate physiological and transport function of various sources of human RPTECs under static and fluidic conditions. We tested TERT1-immortalized RPTECs, including OAT1-, OCT2- and OAT3-overexpressing variants) and two primary RPETC sources. Cells were cultured on transwell membranes in two conditions – static (24-well transwells) and fluidic (transwells placed into PhysioMimix TC12 organ-on-chip platform with 2 L/s flow). We evaluated barrier formation, transport, and gene expression. We show that primary RPTECs may not be suitable for studies of directional transport on transwell membranes because they form an inferior barrier even though they show generally more relevant expression of key transporters, especially when shear stress is present. Both TERT1 and -OAT1 and -OAT3 overexpressing cells formed robust barrier, but it was unaffected by shear stress. TERT1-OAT1 cells exhibited inhibitable pAH transport; shear stress increased pAH transport function of these cells. However, efficient tenofovir secretion and perfluorooctanoic acid (PFOA) reabsorption by TERT1-OAT1 cells were not modulated by shear stress. With respect to gene expression profiles, we found that both TERT1 and TERT1-OAT1 cells exhibited human kidney-like transcriptomes, but that shear stress did not result in an apparent enhancement of the kidney phenotype. Overall, our data show that addition of flow to in vitro studies of the renal proximal tubule may afford benefits in some aspects of kidney function, but that careful consideration of the impact such studies would have on the cost and throughput of the experiments is needed.
2024-10-23 | GSE246180 | GEO
Project description:Small RNA sequencing of C. elegans mortal germline mutants
| PRJNA522271 | ENA