Overexpression of innate immune response genes in a model of recessive polycystic kidney disease.
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.
Mrug
M
M
Division of Genetic and Translational Medicine, Department of Medicine, The University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL 35294, USA. mmrug@uab.edu.br
Zhou
J
J
Woo
Y
Y
Cui
X
X
Szalai
A J
AJ
Novak
J
J
Churchill
G A
GA
Guay-Woodford
L M
LM
D000818:Animals; D003176:Complement C3 / Q000235:genetics*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000235:genetics*; D007668:Kidney / Q000276:immunology*; D008262:Macrophage Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D015533:Transcriptional Activation
D003176:Complement C3