Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

Biochem Biophys Res Commun. 2005 Apr 1;329(1):275-80. doi: 10.1016/j.bbrc.2005.01.135.


Preferential expression of oncofetal extra domain-B fibronectin (EDB(+) FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB(+) FN expression in endothelial cells (ECs) via transforming growth factor-beta1 (TGF-beta1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB(+) FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-beta1, and ET-1 increase the EDB(+) FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-beta1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB(+) FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB(+) FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB(+) FN expression and provide novel avenues for therapeutic modalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cells, Cultured
  • Diabetic Retinopathy
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / cytology*
  • Enzyme Activation
  • Fibronectins / biosynthesis*
  • Fibronectins / chemistry
  • Fibronectins / metabolism*
  • Gene Silencing
  • Glucose / metabolism*
  • Humans
  • Immediate-Early Proteins
  • Immunoblotting
  • Microcirculation
  • Microscopy, Fluorescence
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1
  • Umbilical Veins / cytology


  • Endothelin-1
  • Fibronectins
  • Immediate-Early Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • oncofetal fibronectin
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Glucose