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

Overview

MeSH Major

  • Epithelial-Mesenchymal Transition
  • Immediate-Early Proteins
  • Protein-Serine-Threonine Kinases
  • Ureteral Obstruction

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.

publication date

  • October 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3935313

Digital Object Identifier (DOI)

  • 10.1038/ki.2010.214

PubMed ID

  • 20631674

Additional Document Info

start page

  • 668

end page

  • 78

volume

  • 78

number

  • 7