Meta-analysis of polycystic kidney disease expression profiles defines strong involvement of injury repair processes.
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 aPkd1-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 anotherPkd1-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.
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; and.
Tareq B
TB
Malas
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; and.
Chiara
C
Formica
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; and.
Wouter N
WN
Leonhard
GenomeScan, Leiden, The Netherlands.
Pooja
P
Rao
GenomeScan, Leiden, The Netherlands.
Zoraide
Z
Granchi
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; and.
Marco
M
Roos
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; and.
Dorien J M
DJ
Peters
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; and p.a.c.hoen@lumc.nl.
Peter A C
PA
't Hoen
D058186:Acute Kidney Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D057225:Data Mining; D030541:Databases, Genetic; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012038:Regeneration / Q000187:drug effects / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000235:genetics; D059467:Transcriptome
D050396:TRPP Cation Channels
Meta-analysis; RNASeq; expression signature; injury repair; literature mining; polycystic kidney disease