Gene expression profiles of renal tubules in the kidney of fibrosis model rat produced by allopurinol.
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE214358 | GEO | 2022/12/31
REPOSITORIES: GEO
Similar Datasets
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:Immunohistochemical Investigation for Renal Tubules in Adaptive and Maladaptive Repair Process after Renal Tubular Injury in the Kidney of Rats
| PRJNA624162 | ENA
Project description:Gene expression profiles of renal tubules in the kidney of fibrosis model rat produced by allopurinol.
| PRJNA885064 | ENA
Project description:Mammalian kidney has very limited ability to repair or regenerate after acute kidney injury (AKI). The maladaptive repair of AKI promotes the progression to chronic kidney disease (CKD). Therefore, it is extremely urgent to explore new strategies to promote the repair/regeneration of injured renal tubules after AKI. It has been shown that hypoxia induces heart regeneration in adult mice. However, it is unknown whether hypoxia can induce kidney regeneration after AKI. In this study, we used a prolyl hydroxylase domain inhibitor (PHDI), MK-8617, to mimic hypoxia condition and found that MK-8617 significantly ameliorates ischemia reperfusion injury (IRI) induced acute kidney injury. We then showed that MK-8617 dramatically facilitates renal regeneration via promoting the proliferation of injured renal proximal tubular cells (RPTCs) after IRI-induced AKI. We then performed bulk mRNA sequencing and discovered that multiple nephrogenesis- related genes were significantly upregulated with MK-8617 pretreatment. Furthermore, we showed that MK-8617 may alleviate proximal tubule injury via stabilizing HIF-1α protein specifically in renal proximal tubular cells. We also demonstrated that MK-8617 promotes the reprogramming of renal proximal tubular cells to Sox9+ renal progenitor cells, and the regeneration of renal proximal tubules. In summary, we discovered that inhibition of prolyl hydroxylase improves renal proximal tubule regeneration after IRI-induced AKI via promoting the reprogramming of renal proximal tubular cells to Sox9+ renal progenitor cells.
2024-10-10 | GSE247560 | 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:We investigated the gene expression profiles of RNA isolated from kidney glomeruli and renal tubules from aged, 24 week old type-2 diabetic (db/db) and non-diabetic mice
2021-09-29 | GSE184836 | GEO
Project description:The adult kidney has a remarkable capacity for self-renewal upon damage. Whether this regeneration is mediated by dedifferentiating surviving cells or as recently suggested by stem cells has not been unequivocally settled. The stem cell concept is however hampered by lack of consensus regarding the histological localization of and defining markers for these cells. Here, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor-like characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDHhigh and ALDHlow cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population with a scattered distribution in the epithelial layer of the proximal tubules (PT). The cells differed from the surrounding cells by expression of CD133, CD24, vimentin, KRT7, KRT19, and BCL2, and were negative for PT-specific markers. Based on functional and bioinformatic analyses as well as an immunophenotypical resemblance to cells of regenerating tubules we suggest that these cells are endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules. The rare intratubular cells also displayed marked transcriptional and immunophenotypical similarities to that of cortical adenomas and papillary renal cell carcinomas, indicating that these renal neoplasms arise through oncogenic transformation of this subset of PT cells. Total RNA extracted from three pairs of ALDH-high and ALDH-low cell fractions were hybridized to Illumina humanHT-12 v3.0 Expression BeadChips (Illumina Inc) at the SCIBLU Genomics Centre at Lund University Sweden (http://www.lth.se/sciblu).
2010-11-01 | E-GEOD-23911 | biostudies-arrayexpress
Project description:The adult kidney has a remarkable capacity for self-renewal upon damage. Whether this regeneration is mediated by dedifferentiating surviving cells or as recently suggested by stem cells has not been unequivocally settled. The stem cell concept is however hampered by lack of consensus regarding the histological localization of and defining markers for these cells. Here, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor-like characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDHhigh and ALDHlow cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population with a scattered distribution in the epithelial layer of the proximal tubules (PT). The cells differed from the surrounding cells by expression of CD133, CD24, vimentin, KRT7, KRT19, and BCL2, and were negative for PT-specific markers. Based on functional and bioinformatic analyses as well as an immunophenotypical resemblance to cells of regenerating tubules we suggest that these cells are endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules. The rare intratubular cells also displayed marked transcriptional and immunophenotypical similarities to that of cortical adenomas and papillary renal cell carcinomas, indicating that these renal neoplasms arise through oncogenic transformation of this subset of PT cells.
2011-02-01 | GSE23911 | GEO
Project description:Nature exploits cage-like proteins for a variety of biological purposes from molecular packaging and cargo delivery to catalysis. These cage-like proteins are of immense importance in nanomedicine due to their propensity to self-assemble from simple identical building blocks to highly-ordered architecture and the design flexibility afforded by protein engineering. However, delivery of protein nanocages to the renal tubules remains a major challenge because of the glomerular filtration barrier, which effectively excludes conventional size nanocages. Here we show that DNA-binding Protein from Starved cells (Dps)—the extremely small archaeal antioxidant nanocage—is able to cross the glomerular filtration barrier and is endocytosed by the renal proximal tubules. Using a model of endotoxemia, we present an example of the way in which proximal tubule-selective Dps nanocage can limit the degree of endotoxin-induced kidney injury. This was accomplished by amplifying the endogenous antioxidant property of Dps with addition of a dinuclear manganese cluster. Dps is the first-in-class, protein cage nanoparticle that can be targeted to renal proximal tubules through glomerular filtration. In addition to its therapeutic potential, chemical and genetic engineering of Dps will offer a novel nanoplatform to advance our understanding of the physiology and pathophysiology of glomerular filtration and tubular endocytosis.
2019-05-30 | GSE131922 | GEO
Project description:We generated primary cultures from renal cell carcinoma and matched normal primary kidney cortex tubule cell cultures from 3 patients. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-seq) and gene expression profiling (RNA-seq). Studying these paired and patient-matched controlled data sets will shed light on the epigenomic changes that underlie transformation of kidney tubules into malignant cancers.
2018-07-19 | GSE117323 | GEO