Snail1 is involved in the renal epithelial-mesenchymal transition

Snail1 is involved in the renal epithelial-mesenchymal transition
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DOI:
10.1016/j.bbrc.2007.07.146
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发表时间:
2007-10-12
影响因子:
3.1
通讯作者:
Hayashi, Matsuhiko
Hayashi, Matsuhiko
中科院分区:
生物学4区
文献类型:
--
作者:
Yoshino, Jun;Monkawa, Toshiaki;Hayashi, Matsuhiko

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肾小管上皮-间质转化(epithelial-mesenchymal transition, EMT)在肾脏疾病中的病理意义日益被认识,而转录因子snail在EMT中起着至关重要的作用。本研究结果显示,单侧输尿管梗阻大鼠肾小管上皮细胞和tgf - β 1处理的人近端肾小管hcc -8细胞中snail mRNA和蛋白表达上调。糖原合成酶激酶-3 β (GSK-3 β)通过降解蜗牛蛋白调节蜗牛水平。在梗阻肾小管上皮细胞中磷酸化无活性形式GSK-3 β水平升高。tgf - β 1增加了HKC-8细胞中GSK-3 β的磷酸化形式,而选择性抑制剂锂和TDZD-8对GSK-3 β的抑制导致了snail蛋白的积累。本研究表明snail参与肾小管EMT, tgf - β 1在转录和蛋白质降解水平上调控snail。(c) 2007爱思唯尔公司版权所有。
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.