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

M. Mrug*, J. Zhou, Y. Woo, X. Cui, A. J. Szalai, J. Novak, G. A. Churchill, L. M. Guay-Woodford

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)63-76
Number of pages14
JournalKidney International
Issue number1
StatePublished - Jan 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank Kassie Johnson for help with generation of the mice and helpful discussions, and Lea Novak, MD, for help with histopathological evaluation of stained tissues. This work was supported by the Polycystic Kidney Disease Foundation Fellowship Award (MM), the National Institutes of Health (MM, GAC, and LGW), Pilot and Feasibility study from UAB Recessive PKD Core Center P30 DK074038 (MM), and R01 DK55534 (LGW), and Clinical Scientist Award in Translational Research from the Burroughs-Wellcome Foundation (LGW).


  • Complement
  • Innate immune response
  • Microarray
  • Recessive PKD
  • cpk mouse

ASJC Scopus subject areas

  • Nephrology


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