Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA131691 | ENA |
REPOSITORIES: ENA
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Project description:Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys, at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5 fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found 9 pathways in common between 3-day and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated 'VDR/RXR Activation,' 'LPS/IL-1 Mediated Inhibition of RXR Function,' and 'LXR/RXR Activation'. These results suggest that RXR mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the up-regulation of Ptx2, Alox15b, OSP and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed both in nuclei and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.
2011-12-09 | GSE23079 | GEO
Project description:Han:SPRD rats carry a missense mutation in Anks6 (also called Pkdr1), leading to an R823W substitution in SamCystin, a protein that contains ankyrin repeats and a sterile alpha motif (SAM). Han:SPRD Cy/+ rats develop a slowly progressing form of PKD which resembles phenotypically human ADPKD. We used microarrays to examine alterations in the renal gene expression in a rodent model of PKD, namely the Han:SPRD rat.
2015-12-02 | GSE75578 | GEO
Project description:To understand the molecular and cellular mechanisms of pathogenesis of autosomal recessive polycystic kidney disease , we performed a microarray gene expression profiling in early stage kidneys of B6C3Fe a/a-bpck mutant and wild-type mice at postnatal day 3. Genes with over 1.5-fold expression changes in mutant kidneys compared with age matched wild-type tissues were selected for analysis. This study represents the first widespread profiling of B6C3Fe a/a-bpck mutant mouse kidney and provides a valuable platform for better understanding the molecular mechanisms of polycystic kidney disease in human.
2011-12-01 | GSE34051 | GEO
Project description:Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments. The Lewis Polycystic Kidney (LPK) rat phenotype has been characterized and classified as a model of nephronophthisis (NPHP9, caused by mutation of the Nek8 gene) for which polycystic kidneys are one of the main pathologic features. The aim of this study was to use a GC-MS-based untargeted metabolomics approach to determine key biochemical changes in kidney and liver tissue of the LPK rat. Tissues from 16-week old LPK (n = 10) and Lewis age- and sex-matched control animals (n = 11) were used. Principal component analysis (PCA) distinguished signal corrected metabolite profiles from Lewis and LPK rats for kidney (PC-1 77%) and liver (PC-1 46%) tissue. There were marked differences in the metabolite profiles of the kidney tissues with 122 deconvoluted features significantly different between the LPK and Lewis strains. The metabolite profiles were less marked between strains for liver samples with 30 features significantly different. Five biochemical pathways showed three or more significantly altered metabolites: transcription/translation, arginine and proline metabolism, alpha-linolenic and linoleic acid metabolism, the citric acid cycle, and the urea cycle. The results of this study validate and complement the current literature and are consistent with the understood pathobiology of PKD.
2023-01-26 | MTBLS748 | MetaboLights
Project description:Gender has strong impact on kidney performance. Female gender tends to be renal protective. PKD/Mhm is rat model for human polycystic kidney disease (PKD) caused by a mutation in gene Anks6. PKD progresses faster in male rats compared with females. We used microarrays to detect gender-dependent gene expression in kidney of 36d old PKD/Mhm rats. Keywords: gender, genotype
2009-09-30 | GSE13065 | GEO
Project description:Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in the ADPKD genes PKD1 and PKD2 account for nearly all the cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1, the product of PKD1, regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product of PKD2. Recently, it was reported that as with polycystin-1, polycystin-2 can acts as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2. In this study we utilized different kidney cell lines expressing wild-type and mutant PKD2 as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation. Surprisingly, over-expression of wild-type PKD2 in renal cell lines failed to inactivate Cdk2 activity and consequently had no effect on cell proliferation. On the other hand, expression of mutated PKD2 augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of STAT-1/p21 pathway. Genome-wide expression analysis in these cells revealed that expression of the cyclin-dependent kinase inhibitor, p57 is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels. Our results indicate the probable involvement of p57 on epithelial cell proliferation in polycystic kidney disease. In addition, it confirms that PKD2-induced proliferation is a multifactorial process. We used microarrays to study the modulation of gene expression by mutated PKD2 in the primary tubular epithelial cells of a transgenic rat mode Keywords: transgene Gene expression in the primary tubular epithelial of a transgenic rat mode with mutated PKD2 was compared with that of SD control rats
2010-05-19 | E-GEOD-11500 | biostudies-arrayexpress
Project description:Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters. Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0,6 and 24 days after birth) we performed gene expression profiling of kidney cells.
2010-01-31 | E-GEOD-19460 | biostudies-arrayexpress
Project description:To understand the molecular and cellular mechanisms of pathogenesis of autosomal recessive polycystic kidney disease , we performed a microarray gene expression profiling in early stage kidneys of B6C3Fe a/a-bpck mutant and wild-type mice at postnatal day 3. Genes with over 1.5-fold expression changes in mutant kidneys compared with age matched wild-type tissues were selected for analysis. This study represents the first widespread profiling of B6C3Fe a/a-bpck mutant mouse kidney and provides a valuable platform for better understanding the molecular mechanisms of polycystic kidney disease in human. Mutational analysis was performed in accordance with the protocol of Jackson Laboratory, total RNA was extracted from kidneys of 3 days of postnatal age using a monophasic solution of phenol/guanidine isothiocyanate and TRIzol reagent (Invitrogen) according to their manual, and the samples were incubated with RNase-free DNase I (Ambion). The quality and concentration of each sample were confirmed by spectrophotometry. Affymetrix 430 2.0 arrays were used according to standard Affymetrix procedures. Data analysis was performed with dChip software (Dec.2010 version). These measurements were confirmed by Real-Time PCR.
2011-12-01 | E-GEOD-34051 | biostudies-arrayexpress
Project description:Gender has strong impact on kidney performance. Female gender tends to be renal protective. PKD/Mhm is rat model for human polycystic kidney disease (PKD) caused by a mutation in gene Anks6. PKD progresses faster in male rats compared with females. We used microarrays to detect gender-dependent gene expression in kidney of 36d old PKD/Mhm rats. Experiment Overall Design: Gender-dependent gene expression was examined both in heterozygous PKD/Mhm rats affected with PKD and in their wild type littermates. Three microarrays were hybridized for each combination of gender and genotype.
2009-10-11 | E-GEOD-13065 | biostudies-arrayexpress
Project description:Polycystic Kidney Disease (PKD) is a genetic disease of the kidney characterized by the gradual replacement of normal kidney parenchyma by fluid-filled cysts and fibrotic tissue. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene. Here we present an RNASeq experiment designed to investigate the effect of a kidney specific and Tamoxifen inducible knockout of the Pkd1 gene in mice. 7 mice were grouped into two groups, 4 Tamoxifen treated mice which develop an adult onset Polycystic Kidney Disease phenotype and 3 untreated mice which have WT phenotype.
2016-06-01 | E-MTAB-4086 | biostudies-arrayexpress