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Biochem Biophys Res Commun. 2007 Oct 12;362(1):63-68. doi: 10.1016/j.bbrc.2007.07.146. Epub 2007 Aug 3.

Snail1 is involved in the renal epithelial-mesenchymal transition.

Author information

1
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
2
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: monkawa@sc.itc.keio.ac.jp.

Abstract

The pathological significance of the tubular epithelial-mesenchymal transition (EMT) in kidney diseases is becoming increasingly recognized, and the transcription factor Snail1 plays a critical role in EMT. The results of this study show that Snail1 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-beta1. Glycogen synthase kinase-3beta (GSK-3beta) regulates the Snail1 level by degrading Snail1 protein. The level of the phosphorylated inactive form of GSK-3beta was increased in the tubular epithelial cells of the obstructed kidney. TGF-beta1 increased the phosphorylated form of GSK-3beta in HKC-8 cells, and inhibition of GSK-3beta by the selective inhibitors lithium and TDZD-8 caused Snail1 protein to accumulate. This study demonstrated that Snail1 is involved in renal tubular EMT and that TGF-beta1 regulates Snail1 at the transcription and protein degradation levels.

PMID:
17692821
DOI:
10.1016/j.bbrc.2007.07.146
[Indexed for MEDLINE]

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