Snail1 is involved in the renal epithelial-mesenchymal transition.
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.
Yoshino
Jun
J
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Monkawa
Toshiaki
T
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.
Tsuji
Mihoko
M
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Inukai
Mai
M
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Itoh
Hiroshi
H
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Hayashi
Matsuhiko
M
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008648:Mesoderm / Q000473:pathology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C000604407:SNAI1 protein, human; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3