High glucose induced VEGF expression via PKC and ERK in glomerular podocytes

Biochem Biophys Res Commun. 2002 Jan 11;290(1):177-84. doi: 10.1006/bbrc.2001.6138.


Podocytes are the major site of vascular endothelial growth factor (VEGF) production in the kidney, and up-regulation of VEGF plays a critical role in the progression of diabetic nephropathy. Using a differentiated mouse podocyte cell line, we investigated the roles of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) on the expression of VEGF under high glucose conditions. High glucose induced up-regulation of VEGF mRNA and protein expression in podocytes via activation of PKC (PKC-alpha and -betaII isoforms) and ERK. High glucose stimulated [(3)H]leucine incorporation in the podocytes. High glucose and the PKC stimulator, phorbol 12-myristate 13-acetate (PMA) induced activator protein-1 (AP-1)-dependent transcriptional activity and expression of VEGF. In addition, these phenomena were blocked by specific inhibitors of PKC (GF10902X) and ERK kinase (PD98059). These observations suggested that high glucose-induced VEGF expression in podocytes was largely mediated through PKC and ERK pathways that may be involved in diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Endothelial Growth Factors / biosynthesis*
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Glucose / metabolism
  • Glucose / pharmacology*
  • Kidney / cytology*
  • Kidney / enzymology*
  • Kidney / metabolism
  • Leucine / metabolism
  • Lymphokines / biosynthesis*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / physiology
  • Protein Kinase C / metabolism*
  • Protein Kinase C / physiology
  • RNA, Messenger / metabolism
  • Tetradecanoylphorbol Acetate / metabolism
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Enzyme Inhibitors
  • Flavonoids
  • Lymphokines
  • RNA, Messenger
  • Transcription Factor AP-1
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Leucine
  • Glucose
  • Tetradecanoylphorbol Acetate
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one