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

Abstract

BACKGROUND:

In this study we hypothesised that proliferation, and the increased expression of G(1)-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.

• Authors: Kristina G Schwensen, Jane S Burgess, Nicole S Graf, Stephen I Alexander, David C Harris, Jacqueline K Phillips, Gopala K Rangan
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 117 Issue 4 Pg. e93-103 ( 2011) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 20924203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 S. Karger AG, Basel.

Chemical References

• Ki-67 Antigen
• Retinoblastoma Protein
• Cyclin D1

Topics

• Animals
• Cell Nucleus (metabolism)
• Cell Proliferation
• Cyclin D1 (metabolism)
• Cysts (metabolism, pathology)
• Disease Models, Animal
• Humans
• Immunohistochemistry
• Ki-67 Antigen (metabolism)
• Polycystic Kidney, Autosomal Recessive (metabolism, pathology)
• Rats
• Rats, Inbred Lew
• Retinoblastoma Protein (metabolism)
• Time Factors