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Published on: March 15, 2016

c-Jun and JunB are essential for hypoglycemia-mediated VEGF induction

Björn Textor1, Melanie Sator-Schmitt, Karl Hartmut Richter

  • 1Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

Annals of the New York Academy of Sciences
|March 8, 2007
PubMed

Insights

Hypoglycemia (low blood sugar) triggers vascular endothelial growth factor (VEGF) expression through AP-1 transcription factors c-Jun and JunB. This process is independent of HIF-1 and involves protein kinase C and ERK signaling pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Vascular Endothelial Growth Factor (VEGF) is crucial for angiogenesis, and its expression is induced by physiological conditions like hypoglycemia.
  • The transcription factor Activator Protein-1 (AP-1) plays a role in gene regulation, but its specific involvement in hypoglycemia-induced VEGF expression is not fully understood.

Purpose of the Study:

  • To investigate the role of AP-1 transcription factor subunits, specifically c-Jun and JunB, in the regulation of VEGF expression during hypoglycemia.
  • To elucidate the signaling pathways involved in the activation of c-Jun and JunB under hypoglycemic conditions.

Main Methods:

  • Utilized c-jun(-/-) and junB(-/-) mouse embryonic fibroblasts to assess the necessity of these subunits.
  • Employed specific inhibitors for protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) signaling pathways.
  • Analyzed the impact of AP-1 subunit deficiency on HIF-1 expression and stabilization.

Main Results:

  • Both c-Jun and JunB are essential for hypoglycemia-mediated induction of VEGF expression.
  • The observed VEGF regulation by AP-1 is independent of Hypoxia-Inducible Factor 1 (HIF-1).
  • Hypoglycemia-induced c-Jun activation is dependent on PKCalpha signaling, while JunB activation is mediated by ERK signaling.

Conclusions:

  • AP-1 subunits c-Jun and JunB are key mediators of VEGF expression in response to hypoglycemia.
  • Distinct signaling pathways, PKCalpha for c-Jun and ERK for JunB, converge on AP-1 to regulate VEGF under low glucose conditions.
  • These findings reveal a novel molecular mechanism linking metabolic stress to angiogenesis regulation.

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