Details

Autor(en) / Beteiligte

• Malas, Tareq B
• Formica, Chiara
• Leonhard, Wouter N
• Rao, Pooja
• Granchi, Zoraide
• Roos, Marco
• Peters, Dorien J M
• 't Hoen, Peter A C

Titel

Meta-analysis of polycystic kidney disease expression profiles defines strong involvement of injury repair processes

Ist Teil von

• American journal of physiology. Renal physiology, 2017-04, Vol.312 (4), p.F806-F817

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Polycystic kidney disease (PKD) is a major cause of end-stage renal disease. The disease mechanisms are not well understood and the pathogenesis toward renal failure remains elusive. In this study, we present the first RNASeq analysis of a -mutant mouse model in a combined meta-analysis with other published PKD expression profiles. We introduce the PKD Signature, a set of 1,515 genes that are commonly dysregulated in PKD studies. We show that the signature genes include many known and novel PKD-related genes and functions. Moreover, genes with a role in injury repair, as evidenced by expression data and/or automated literature analysis, were significantly enriched in the PKD Signature, with 35% of the PKD Signature genes being directly implicated in injury repair. NF-κB signaling, epithelial-mesenchymal transition, inflammatory response, hypoxia, and metabolism were among the most prominent injury or repair-related biological processes with a role in the PKD etiology. Novel PKD genes with a role in PKD and in injury were confirmed in another -mutant mouse model as well as in animals treated with a nephrotoxic agent. We propose that compounds that can modulate the injury-repair response could be valuable drug candidates for PKD treatment.