TY - JOUR
T1 - Snail1 is involved in the renal epithelial-mesenchymal transition
AU - Yoshino, Jun
AU - Monkawa, Toshiaki
AU - Tsuji, Mihoko
AU - Inukai, Mai
AU - Itoh, Hiroshi
AU - Hayashi, Matsuhiko
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research (C), for Young Scientists (B), and for the “High-Tech Research Center” Project for Private Universities from the Education, Culture, Sports, Science, and Technology of Japan, a Health Labour Sciences Research Grant, a Keio University Grant-in-Aid for Encouragement of Young Medical Scientists, and Keio Gijuku Academic Development Funds.
PY - 2007/10/12
Y1 - 2007/10/12
N2 - 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-β1. Glycogen synthase kinase-3β (GSK-3β) regulates the Snail1 level by degrading Snail1 protein. The level of the phosphorylated inactive form of GSK-3β was increased in the tubular epithelial cells of the obstructed kidney. TGF-β1 increased the phosphorylated form of GSK-3β in HKC-8 cells, and inhibition of GSK-3β 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-β1 regulates Snail1 at the transcription and protein degradation levels.
AB - 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-β1. Glycogen synthase kinase-3β (GSK-3β) regulates the Snail1 level by degrading Snail1 protein. The level of the phosphorylated inactive form of GSK-3β was increased in the tubular epithelial cells of the obstructed kidney. TGF-β1 increased the phosphorylated form of GSK-3β in HKC-8 cells, and inhibition of GSK-3β 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-β1 regulates Snail1 at the transcription and protein degradation levels.
KW - Epithelial-mesenchymal transition
KW - Glycogen synthase kinase-3β
KW - Obstructive nephropathy
KW - Renal fibrosis
KW - Renal tubular epithelial cells
KW - Snail1
KW - TGF-β1
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U2 - 10.1016/j.bbrc.2007.07.146
DO - 10.1016/j.bbrc.2007.07.146
M3 - Article
C2 - 17692821
AN - SCOPUS:34548077210
SN - 0006-291X
VL - 362
SP - 63
EP - 68
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
