Snail1 is involved in the renal epithelial-mesenchymal transition

被引:70
|
作者
Yoshino, Jun [1 ]
Monkawa, Toshiaki [1 ]
Tsuji, Mihoko [1 ]
Inukal, Mai [1 ]
Roh, Hiroshi [1 ]
Hayashi, Matsuhiko [1 ]
机构
[1] Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan
关键词
obstructive nephropathy; renal fibrosis; renal tubular epithelial cells; epithelial-mesenchymal transition; glycogen synthase kinase-3 beta; TGF-beta; 1; snail1;
D O I
10.1016/j.bbrc.2007.07.146
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 pathological significance of the tubular epithelial-mesenchymal transition (EMT) in kidney diseases is becoming increasingly recognized, and the transcription factor Snaill plays a critical role in EMT. The results of this study show that Snaill mRNA and protein were upregulated in the tubular epithelial cells of the obstructed kidneys in a rat model of unilateral ureteral obstruction and in human proximal tubule HKC-8 cells treated with TGF-beta 1. Glycogen synthase kinase-3 beta (GSK-3 beta) regulates the Snaill level by degrading Snaill protein. The level of the phosphorylated inactive form of GSK-3 beta was increased in the tubular epithelial cells of the obstructed kidney. TGF-beta 1 increased the phosphorylated form of GSK-3 beta in HKC-8 cells, and inhibition of GSK-3 beta by the selective inhibitors lithium and TDZD-8 caused Snaill protein to accumulate. This study demonstrated that Snaill is involved in renal tubular EMT and that TGF-beta 1 regulates Snaill at the transcription and protein degradation levels. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:63 / 68
页数:6
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