title: Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats.
abstract: OBJECTIVE
  To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD).
  
  
  METHODS
  The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofluorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFα and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue.
  
  
  RESULTS
  Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with α smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBα protein levels, and TNFα and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identified in the CECs of LPK and human polycystic kidneys.
  
  
  CONCLUSIONS
  Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.
authors.affiliation: Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
authors.forename: Michelle H T
authors.initials: MH
authors.lastname: Ta
authors.affiliation: Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
authors.forename: Kristina G
authors.initials: KG
authors.lastname: Schwensen
authors.affiliation: Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Liuwantara
authors.affiliation: Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.affiliation: Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
authors.forename: Terry
authors.initials: T
authors.lastname: Watnick
authors.affiliation: Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Rangan
keywords: Chemokine CCL2; Inflammation; Nuclear factor-κB; Polycystic kidney disease; Tumour necrosis factor alpha