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

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Complement-C3, Disease-Models-Animal, Gene-Expression-Profiling, Immunity-Natural, Kidney, Macrophage-Activation, Male, Mice, Mice-Mutant-Strains, Polycystic-Kidney-Diseases, Trans-Activation-(Genetics)

JAX Source

Kidney Int 2008 Jan; 73(1):63-76.


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.