In:
Nephron Experimental Nephrology, S. Karger AG, Vol. 117, No. 4 ( 2010-10-2), p. e93-e103
Abstract:
〈 i 〉 Background: 〈 /i 〉 In this study we hypothesised that proliferation, and the increased expression of G 〈 sub 〉 1 〈 /sub 〉 -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). 〈 i 〉 Methods: 〈 /i 〉 Lewis polycystic kidney disease 〈 i 〉 (lpk) 〈 /i 〉 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. 〈 i 〉 Results: 〈 /i 〉 Between weeks 1 and 3, the percentage cyst area increased 6-fold in 〈 i 〉 lpk 〈 /i 〉 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 〈 i 〉 lpk 〈 /i 〉 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. 〈 i 〉 Conclusion: 〈 /i 〉 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.
Type of Medium:
Online Resource
ISSN:
1660-2129
Language:
English
Publisher:
S. Karger AG
Publication Date:
2010
detail.hit.zdb_id:
2098337-2
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