title: Overexpression of innate immune response genes in a model of recessive polycystic kidney disease.
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.
authors.affiliation: 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
authors.forename: M
authors.initials: M
authors.lastname: Mrug
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Woo
authors.forename: X
authors.initials: X
authors.lastname: Cui
authors.forename: A J
authors.initials: AJ
authors.lastname: Szalai
authors.forename: J
authors.initials: J
authors.lastname: Novak
authors.forename: G A
authors.initials: GA
authors.lastname: Churchill
authors.forename: L M
authors.initials: LM
authors.lastname: Guay-Woodford
mesh_terms: 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
chemical_list: D003176:Complement C3