Overexpression of innate immune response genes in a model of recessive polycystic kidney disease

Kidney Int. 2008 Jan;73(1):63-76. doi: 10.1038/sj.ki.5002627. Epub 2007 Oct 24.


Defects in the primary cilium/basal body complex of renal tubular cells cause polycystic kidney disease (PKD). To uncover pathways associated with disease progression, we determined the kidney transcriptome of 10-day-old severely and mildly affected cpk mice, a model of recessive PKD. In the severe phenotype, the most highly expressed genes were those associated with the innate immune response including many macrophage markers, particularly those associated with a profibrotic alternative activation pathway. Additionally, gene expression of macrophage activators was dominated by the complement system factors including the central complement component 3. Additional studies confirmed increased complement component 3 protein levels in both cystic and non-cystic epithelia in the kidneys of cpk compared to wild-type mice. We also found elevated complement component 3 activation in two other mouse-recessive models and human-recessive PKD. Our results suggest that abnormal complement component 3 activation is a key element of progression in PKD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complement C3 / genetics*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Immunity, Innate / genetics*
  • Kidney / immunology*
  • Macrophage Activation / genetics
  • Male
  • Mice
  • Mice, Mutant Strains
  • Polycystic Kidney Diseases / genetics*
  • Transcriptional Activation*


  • Complement C3