Overexpression of innate immune response genes in a model of recessive polycystic kidney disease.
Document Type
Article
Publication Date
2008
Keywords
Complement-C3, Disease-Models-Animal, Gene-Expression-Profiling, Immunity-Natural, Kidney, Macrophage-Activation, Male, Mice, Mice-Mutant-Strains, Polycystic-Kidney-Diseases, Trans-Activation-(Genetics)
First Page
63
Last Page
76
JAX Source
Kidney Int 2008 Jan; 73(1):63-76.
Abstract
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.
Recommended Citation
Mrug M,
Zhou J,
Woo Y,
Cui X,
Szalai AJ,
Novak J,
Churchill GA,
Guay WL.
Overexpression of innate immune response genes in a model of recessive polycystic kidney disease. Kidney Int 2008 Jan; 73(1):63-76.