Early cyst growth is associated with the increased nuclear expression of cyclin D1/Rb protein in an autosomal-recessive polycystic kidney disease rat model

Kristina G. Schwensen, Jane S. Burgess, Nicole S. Graf, Stephen I. Alexander, David C. Harris, Jacqueline K. Phillips, Gopala K. Rangan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: In this study we hypothesised that proliferation, and the increased expression of G1-phase cyclins (D1, E) and phosphorylated retinoblastoma protein (p-Rb) is restricted to the early period of synchronized cyst growth in autosomal-recessive polycystic kidney disease (ARPKD). Methods: Lewis polycystic kidney disease (lpk) rats (model of ARPKD; postnatal weeks 1, 3, 6, 12 and 24; n = 6 each) as well as human juvenile cystic renal disease tissue (n = 2) were examined. Results: Between weeks 1 and 3, the percentage cyst area increased 6-fold in lpk rats, followed by a more progressive rise (1.5-fold increase) until week 24. The number of Ki-67-, cyclin D1- and p-Rb-positive cells increased in lpk rats and peaked at week 3, declining thereafter. By serial sections, cysts co-expressed Ki-67, cyclin D1 and p-Rb. The expression of cyclin E was variable, and peaked at week 24. In human tissue, small cysts had a higher expression of p-Rb. Conclusion: Proliferation and the increased nuclear expression of cyclin D1 and p-Rb coincide with the early phase of cyst growth in rats and humans, suggesting that there might be a therapeutic window in which cyclin-dependent kinase inhibitors are most effective in preventing kidney enlargement in ARPKD.

Original languageEnglish
Pages (from-to)E93-E103
Number of pages11
JournalNephron - Experimental Nephrology
Volume117
Issue number4
DOIs
Publication statusPublished - Apr 2011

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