Polycystic kidney disease (PKD) is characterized by cystic expansion of the kidneys, which can lead to kidney failure. PKD affects one in ∼ 1000 people worldwide and is commonly caused by defects in polycystin 1 (PKD1), polycystin 2 (PKD2), or polycystic kidney and hepatic disease 1 (PKHD1). However, there are variability in the symptom and progression of PKD caused by same mutation in these causative genes, suggesting that there may be many other genes involved in the pathogenesis of PKD. In this study, we performed comparative transcriptome analysis of three mammalian PKD datasets (PKD caused by knockout of PKD1, PKHD1, or AQP11) downloaded from a public database. We were able to identify two down-regulated and six up-regulated genes including osteopontin in common among the three different PKD models. In silico analysis of the promoters of these six up-regulated genes revealed that transcription factors HNF4 and RXRA might be involved in the up-regulation of these genes. Osteropontin, HNF4 and RXRA have been associated with the pathogenesis of PKD, supporting the validity of the approach used in this study. We now analyze the relationship between these dysregulated genes and the pathogenesis of PKD using zebrafish.

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