Abstract:
BACKGROUND:Cux-1 is a murine homeodomain protein that functions as a cell cycle-dependent transcriptional repressor in proliferating cells. Targets of Cux-1 repression include the cyclin kinase inhibitors p21 and p27. In the kidney, Cux-1 is spatially and temporally regulated, and ectopic expression of Cux-1 in transgenic mice results in renal hyperplasia. Previously, we observed that Cux-1 is deregulated in cystic kidneys from cpk mice. Recent studies have suggested a role for the cyclin kinase inhibitor p21 in the development of polycystic kidney disease (PKD) in mice lacking PKD1. METHODS:Since p21 is a target of transcriptional repression by Cux-1, we compared the expression of Cux-1 and p21 in kidneys from Pkd1 null and cpk mice by immunohistochemistry and Western blotting. We also evaluated apoptosis and the expression of the cyclin kinase inhibitor p27 in Pkd1 null and cpk mice by terminal deoxynucleotidal transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining, immunohistochemistry, and Western blotting. RESULTS:In both early and late embryonic kidneys from Pkd1 null mice, Cux-1 was highly and ectopically expressed in normal-appearing tubule epithelium, interstitial cells, and in the epithelial cells lining the cysts, where it colocalized with proliferating cell nuclear antigen (PCNA). Increased Cux-1 expression in Pkd1 null kidneys was also associated with a decrease in p27 expression at late stages of cystogenesis. In cpk kidneys, Cux-1 was not up-regulated until late stages of cyst development. Moreover, in contrast to Pkd1 null kidneys, p21 and p27 were highly expressed in cpk kidneys. In late stages of cystogenesis, Cux-1 and p21 colocalized in cyst lining cells, which also showed a high incidence of apoptosis. CONCLUSION:These results suggest that cyst development in Pkd1 null mice and cpk mice proceeds through different mechanisms. In Pkd1 null mice, ectopic expression of Cux-1 is associated with increased cell proliferation. In contrast, in cpk mice, ectopic expression of Cux-1 is associated with apoptosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Sharma M,Brantley JG,Alcalay NI,Zhou J,Heystek E,Maser RL,Vanden Heuvel GBdoi
10.1111/j.1523-1755.2005.67099.xsubject
Has Abstractpub_date
2005-02-01 00:00:00pages
432-42issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)50477-8journal_volume
67pub_type
杂志文章abstract::The Executive Summary of the KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients is presented in this issue of Kidney International. This guideline will require careful attention for implementation in the context of available resources within each country, especially those with underdevelope...
journal_title:Kidney international
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pub_type: 杂志文章,随机对照试验
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更新日期:2017-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2016-03-01 00:00:00
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pub_type: 杂志文章
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journal_title:Kidney international
pub_type: 杂志文章
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更新日期:1999-12-01 00:00:00
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更新日期:2001-01-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
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更新日期:2015-05-01 00:00:00
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journal_title:Kidney international
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更新日期:2017-09-01 00:00:00
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pub_type: 评论,杂志文章
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