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

M. Mrug*, J. Zhou, Yong 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

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)63-76
Number of pages14
JournalKidney International
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

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

ASJC Scopus subject areas

  • Nephrology

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