Gene profiling of polycystic kidneys

Nephrol Dial Transplant. 2006 Jul;21(7):1816-24. doi: 10.1093/ndt/gfl071. Epub 2006 Mar 6.


Background: While the genetic basis of autosomal dominant polycystic kidney disease (ADPKD) has been clearly established, the pathogenesis of renal failure in ADPKD remains elusive. Cyst formation originates from proliferating renal tubular epithelial cells that de-differentiate. Fluid secretion with cyst expansion and reactive changes in the extracellular matrix composition combined with increased apoptosis and proliferation rates have been implicated in cystogenesis.

Methods: To identify genes that characterize pathogenical changes in ADPKD, we compared the expression profiles of 12 ADPKD kidneys, 13 kidneys with chronic transplant nephropathy and 16 normal kidneys using a 7 k cDNA microarray. RT-PCR and immunohistochemical techniques were used to confirm the microarray data.

Results: Hierarchical clustering revealed that the gene expression profiles of normal, ADPKD and rejected kidneys were clearly distinct. A total of 87 genes were specifically regulated in ADPKD; 26 of these 87 genes were typical for smooth muscle, suggesting epithelial-to-myofibroblast transition (EMT) as a pathogenetic factor in ADPKD. Immunohistology revealed that smooth muscle actin, a typical marker for myofibroblast transition, and caldesmon were mainly expressed in the interstitium of ADPKD kidneys. In contrast, up-regulated keratin 19 and fibulin-1 were confined to cystic epithelia.

Conclusion: Our results show that the end stage of ADPKD is associated with increased markers of EMT, suggesting that EMT contributes to the progressive loss of renal function in ADPKD.

MeSH terms

  • Cluster Analysis
  • DNA, Complementary / metabolism
  • Disease Progression
  • Epithelium / metabolism
  • Gene Expression Profiling*
  • Genetic Predisposition to Disease
  • Humans
  • Kidney / metabolism*
  • Mesoderm / metabolism
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Polycystic Kidney Diseases / genetics*
  • Polycystic Kidney Diseases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA, Complementary