Identification of ADPKD-related Genes and Pathways in the Cells Overexpressing PKD2
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA593205 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10582015_1.fastq.gz | Fastqsanger.gz | |||
| SRR10582015_2.fastq.gz | Fastqsanger.gz | |||
| SRR10582016_1.fastq.gz | Fastqsanger.gz | |||
| SRR10582016_2.fastq.gz | Fastqsanger.gz | |||
| SRR10582017_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Based on the dosage effect hypothesis, renal cysts could arise in transgenic murine models overexpressing either PKD1 or PKD2, which are causal genes responsible for autosomal dominant polycystic kidney disease (ADPKD). To prove whether PKD genes overexpression is a universal mechanism driving cystogenesis or is merely restricted to rodents, other animal models are required. Previously, we failed to observe any renal cysts in a PKD2 overexpression transgenic pig model partially due to epigenetic silencing of transgene. Thus, to explore the feasibility of pig models and identification potential affected genes/pathways related to ADPKD, LLC-PK1 cells with high PKD2 expression were generated. RNA-seq was performed and MYC, IER3, ADM were found to be commonly upregulated genes in different PKD2 overexpression cell models. MYC is a well-characterized factor contributing to cystogenesis, and ADM is a biomarker for chronic kidney disease. Thus, theses genes might be indicators of disease progression. Additionally, some ADPKD associated pathways, e.g., MAPK, were also enriched in the cells. Besides, GO analysis demonstrated proliferation, apoptosis, cell cycle regulation, which are hall marks of ADPKD were disturbed. Therefore, our experiment not only identified some biomarkers or indictors regarding ADPKD, but also demonstrated high PKD2 expression would like to drive cystogenesis in future porcine models.
2019-12-04 | GSE141355 | GEO
Project description:PKD2 Arg803* is the most common mutation in Taiwan ADPKD Cohort. Genotyping of 96 PKD2 Arg803* individuals was performed in Axiom Genome-Wide TWB 2.0 Array Plate to study the existence of founder mutation in Taiwan
2022-06-07 | E-MTAB-11846 | biostudies-arrayexpress
Project description:Consistent with the gene dosage effect hypothesis, renal cysts can arise in transgenic murine models overexpressing either PKD1 or PKD2, which are causal genes for autosomal dominant polycystic kidney disease (ADPKD). To determine whether PKD gene overexpression is a universal mechanism driving cystogenesis or is merely restricted to rodents, other animal models are required. Previously, we failed to observe any renal cysts in a transgenic porcine model of PKD2 overexpression partially due to epigenetic silencing of the transgene. Thus, to explore the feasibility of porcine models and identify potential genes/pathways affected in ADPKD, LLC-PK1 cells with high PKD2 expression were generated. mRNA sequencing (RNA-seq) was performed, and MYC, IER3, and ADM were found to be upregulated genes common to the different PKD2 overexpression cell models. MYC is a well-characterized factor contributing to cystogenesis, and ADM is a biomarker for chronic kidney disease. Thus, these genes might be indicators of disease progression. Additionally, some ADPKD-associated pathways, e.g., the mitogen-activated protein kinase (MAPK) pathway, were enriched in the cells. Moreover, gene ontology (GO) analysis demonstrated that proliferation, apoptosis, and cell cycle regulation, which are hallmarks of ADPKD, were altered. Therefore, our experiment identified some biomarkers or indicators of ADPKD, indicating that high PKD2 expression would likely drive cystogenesis in future porcine models.
| S-EPMC7074416 | biostudies-literature
Project description:We performed unbiased transcriptional profiling in an adult-onset Pkd2 mouse model at an early stage before cysts formed using as controls wild type and PC2+cilia double knockout mice which are protected from ADPKD. By a tripartite comparison, we identified differetially expressed genes which have significant different expression in Pkd2-only knockout with same direction of change from both wild type and Pkd2+Cilia double knockout.
2020-12-31 | GSE149739 | GEO
Project description:Purpose: Determine the differential gene expression pattern between wildtype, Pkd2-KO and Pkd2-miR-214 KO mice Methods: kidney mRNA profiles of Pkd2-KO and Pkd2-mir-214-KO mice was sequenced with N of 3 in each group Results: 972 differentially expressed transcripts were identified between Pkd2-KO kidneys and Pkd2-miR-214-KO kidneys Conclusion: Deletion of miR-214 promotes interstitial inflammation in mouse models of ADPKD
2019-09-25 | GSE137945 | GEO
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:Changes in gene expression levels were identified by microarray. Samples were human kidney epithelial cell lines derived from patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and unaffected controls. Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most common inherited kidney disease, is due to mutations in PKD1 (85%) or PKD2 (15%) but has a highly variable phenotypic disease expression. We conducted parallel microarray profiling in normal and diseased human PKD1 cystic kidney cells to identify altered signatures of microRNA and mRNA target genes potentially implicated in disease expression.
2017-07-05 | E-MTAB-4188 | 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.
2010-02-01 | GSE19460 | GEO
Project description:Changes in microRNA expression levels were identified by microarray. Samples were human kidney epithelial cell lines derived from patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and unaffected controls. Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most common inherited kidney disease, is due to mutations in PKD1 (85%) or PKD2 (15%) but has a highly variable phenotypic disease expression. We conducted parallel microarray profiling in normal and diseased human PKD1 cystic kidney cells to identify altered signatures of microRNA and mRNA target genes potentially implicated in disease expression. This dataset contains the results of the microRNA analysis.
2017-07-05 | E-MTAB-4189 | biostudies-arrayexpress
Project description:Transcriptional profiling in adult onset ADPKD mouse model based on Pkd2 inactivation
| PRJNA629819 | ENA