The cyclin-dependent kinase inhibitor p21 is essential for the beneficial effects of renal ischemic preconditioning on renal ischemia/reperfusion injury in mice

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27459
Title
The cyclin-dependent kinase inhibitor p21 is essential for the beneficial effects of renal ischemic preconditioning on renal ischemia/reperfusion injury in mice
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Description

Abstract

The cyclin-dependent kinase inhibitor p21 plays important roles in chronic renal disorders; however, its roles in response to acute renal stress are unclear. Here we evaluated p21 in acute kidney injury and ischemic preconditioning using wild-type and p21 knockout mice that underwent renal ischemia followed by reperfusion. The decline in renal function and histological changes were worse in the knockout than in wild-type mice. Ischemia/reperfusion increased p21 expression in the kidney of wild-type mice compared with sham surgery, suggesting p21 may confer tolerance to ischemia/reperfusion injury. We next tested whether p21 is associated with the protective effect of ischemic preconditioning, an established method to reduce ischemia/reperfusion injury. Ischemic preconditioning attenuated ischemia/reperfusion injury in wild-type but not p21-knockout mice. This preconditioning decreased the number of proliferating tubular cells before but increased them at 24 h after ischemia/reperfusion in the kidneys of wild-type mice. In p21-knockout mice, ischemic preconditioning did not change the number of proliferating cells before but decreased them after ischemia/reperfusion. Ischemic preconditioning increased renal p21 expression and the number of cells in the G1 phase of the cell cycle before ischemia/reperfusion compared with sham surgery. Thus, renal p21 is essential for the beneficial effects of renal ischemic preconditioning. Transient cell cycle arrest induced by ischemic preconditioning by a p21-dependent pathway seems to be important for subsequent tubular cell proliferation after ischemia/reperfusion.

(医博甲576)

Author
著者 西岡 聡
著者(ヨミ) ニシオカ サトシ
著者(別表記) Nishioka Satoshi
Publication Title
Kidney International
Publication Title Alternative
Kidney Int.
Volume
85
Issue
4
Start Page
871
End Page
879
Publisher
International Society of Nephrology
Elsevier
Published Date
2013-12-11
ISSN
0085-2538
NCID
AA00711004
PMID
24336034
DOI
10.1038/ki.2013.496
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1038/ki.2013.496
Text Version
none
Grant ID
博甲第576号
Grant Date
2013-12-26
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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