Snail1 is involved in the renal epithelial-mesenchymal transition

Jun Yoshino, Toshiaki Monkawa, Mihoko Tsuji, Mai Inukai, Hiroshi Itoh, Matsuhiko Hayashi

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume362
Issue number1
DOIs
Publication statusPublished - 2007 Oct 12

Keywords

  • Epithelial-mesenchymal transition
  • Glycogen synthase kinase-3β
  • Obstructive nephropathy
  • Renal fibrosis
  • Renal tubular epithelial cells
  • Snail1
  • TGF-β1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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