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.