Cyclin I protects podocytes from apoptosis

被引:48
作者
Griffin, Sian V.
Olivier, J. Paul
Pippin, Jeffrey W.
Roberts, James M.
Shankland, Stuart J. [1 ]
机构
[1] Univ Washington, Sch Med, Dept Med, Div Nephrol, Seattle, WA 98195 USA
[2] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA
关键词
D O I
10.1074/jbc.M513336200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The limited regenerative capacity of the glomerular podocyte following injury underlies the development of glomerulosclerosis and progressive renal failure in a diverse range of kidney diseases. We discovered that, in the kidney, cyclin I is uniquely expressed in the glomerular podocyte, and have constructed cyclin I knock-out mice to explore the biological function of cyclin I in these cells. Cyclin I knock-out (-/-) podocytes showed an increased susceptibility to apoptosis both in vitro and in vivo. Following induction of experimental glomerulonephritis, podocyte apoptosis was increased 4-fold in the cyclin I -/- mice, which was associated with dramatically decreased renal function. Our previous data showed that the Cdk inhibitor p21(Cip1/Waf1) protects podocytes from certain apoptotic stimuli. In cultured cyclin I -/- podocytes, the level of p21(Cip1/Waf1) was lower at base line, had a shorter half-life, and declined more rapidly in response to apoptotic stimuli than in wild- type cells. Enforced expression of p21(Cip1/Waf1) reversed the susceptibility of cyclin I -/- podocytes to apoptosis. Cyclin I protects podocytes from apoptosis, and we provide preliminary data to suggest that this is mediated by stabilization of p21(Cip1/Waf1).
引用
收藏
页码:28048 / 28057
页数:10
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