Transcriptomics

Dataset Information

33

Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways


ABSTRACT: 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. Overall design: 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.

INSTRUMENT(S): Affymetrix GeneChip Rat Genome 230 2.0 Array (CDF: Rat2302_Rn_ENTREZG.cdf version 12.0.0)

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Carsten Sticht 

PROVIDER: GSE19460 | GEO | 2010-02-01

SECONDARY ACCESSION(S): PRJNA120329

REPOSITORIES: GEO

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