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

• DOI: 10.1038/sj.ki.5002627
• Publication Date: 2007-10-24T13:26:19Z
• Authors: M. Mrug; J. Zhou; Y. Woo; X. Cui; A.J. Szalai; J. Novak; G.A. Churchill; L.M. Guay-Woodford
• Keywords: Complement component 3

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.