The cyclin-dependent kinase inhibitor p21 is essential for the beneficial effects of renal ischemic preconditioning on renal ischemia/reperfusion injury in mice
URI | http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27459 | ||||||
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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) |
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Author |
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Publication Title |
Kidney International
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Publication Title Alternative |
Kidney Int.
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Volume |
85
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Issue |
4
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Start Page |
871
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End Page |
879
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Publisher |
International Society of Nephrology
Elsevier
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Published Date |
2013-12-11
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ISSN |
0085-2538
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NCID |
AA00711004
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PMID |
24336034
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DOI |
10.1038/ki.2013.496
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Resource Type |
Thesis or Dissertation
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Language |
eng
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Resource URL |
https://doi.org/10.1038/ki.2013.496
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Text Version |
none
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Grant ID |
博甲第576号
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Grant Date |
2013-12-26
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Degree Name |
博士(医学)
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Grantor |
香川大学
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Set |
香川大学
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