Serum- and glucocorticoid-regulated kinase 1 is upregulated following unilateral ureteral obstruction causing epithelial-mesenchymal transition

Jizhong Cheng, Luan Truong, Xiaoqian Wu, Dietmar Kuhl, Florian Lang, Jie Du

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Obstructive nephropathy leads to chronic kidney disease, characterized by a progressive epithelial-to-mesenchymal cell transition (EMT)-driven interstitial fibrosis. To identify the mechanisms causing EMT, we used the mouse model of unilateral ureteral obstruction and found a rapid and significant increase in serum- and glucocorticoid-regulated kinase-1 (SGK1) expression in the kidneys with an obstructed ureter. Knockout of SGK1 significantly suppressed obstruction-induced EMT, kidney fibrosis, increased glycogen synthase kinase-3Β activity, and decreased accumulation of the transcriptional repressor Snail. This caused a reduced expression of the mesenchymal marker α-smooth muscle actin, and collagen deposition in this model. In cultured kidney epithelial cells, mechanical stretch or treatment with transforming growth factor-Β not only stimulated the transcription of SGK1, but also stimulated EMT in an SGK1-dependent manner. Activated SGK1 stimulated Snail accumulation and downregulation of the epithelial marker E-cadherin. Hence, our study shows that SGK1 is involved in mediating fibrosis associated with obstructive nephropathy.

Original languageEnglish (US)
Pages (from-to)668-678
Number of pages11
JournalKidney international
Volume78
Issue number7
DOIs
StatePublished - Oct 2010

Keywords

  • epithelial-to-mesenchymal transition
  • fibrosis
  • glycogen synthase kinase
  • obstructive nephropathy
  • SGK1
  • Snail

ASJC Scopus subject areas

  • Nephrology

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