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Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/116190
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- Title
- Early cyst growth is associated with the increased nuclear expression of cyclin D1/Rb protein in an autosomal-recessive polycystic kidney disease rat model
- Related
- Nephron : Experimental Nephrology, Vol. 117, Issue 4 (2011), p.e93-e103
- DOI
- 10.1159/000320149
- Publisher
- Karger
- Date
- 2011
- Author/Creator
- Schwensen, Kristina G
- Author/Creator
- Burgess, Jane S
- Author/Creator
- Graf, Nicole S
- Author/Creator
- Alexander, Stephen I
- Author/Creator
- Harris, David C
- Author/Creator
- Phillips, Jacqueline K
- Author/Creator
- Rangan, Gopala K
- Description
- 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.
- Description
- 10 page(s)
- Subject Keyword
- 111600 Medical Physiology
- Subject Keyword
- polycystic kidney disease
- Subject Keyword
- proliferation
- Subject Keyword
- cyclin
- Resource Type
- journal article
- Organisation
- Macquarie University. Australian School of Advanced Medicine
- Identifier
- http://hdl.handle.net/1959.14/116190
- Identifier
- mq:12402
- Identifier
- ISSN:1018-7782
- Identifier
- mq-rm-2010004013
- Language
- eng
- Reviewed
Macquarie University ResearchOnline
