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Related Experiment Videos

VEGF differentially activates STAT3 in microvascular endothelial cells.

Manuela Bartoli1, Dan Platt, Tahira Lemtalsi

  • 1Vascular Biology Center, CB 3209, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912, USA. mbartoli@mail.mcg.edu

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 26, 2003
PubMed
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Vascular Endothelial Growth Factor (VEGF) activates Signal Transducer and Activator of Transcription 3 (STAT3) in microvascular cells, promoting angiogenesis. This STAT3 activation is linked to VEGF receptor 2 (VEGFR2) complex formation and stimulates VEGF gene expression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Angiogenesis Research

Background:

  • Vascular Endothelial Growth Factor (VEGF) plays a critical role in angiogenesis, a process often dysregulated in various pathologies.
  • Signal Transducer and Activator of Transcription 3 (STAT3) is known to mediate VEGF gene transcription and activation.

Purpose of the Study:

  • To investigate the differential activation of STAT3 by VEGF in microvascular versus macrovascular endothelial cells.
  • To elucidate the role of VEGFR2/STAT3 complex formation in VEGF-induced autocrine signaling and gene expression.

Main Methods:

  • Western analysis and confocal immunocytochemistry to assess STAT3 activation in retinal microvascular endothelial cells (BREC).
  • Immunoprecipitation assays to detect VEGF complex formation with VEGFR2.

Related Experiment Videos

  • Quantitative real-time RT-PCR to measure VEGF mRNA expression.
  • Antisense-mediated reduction of STAT3 to evaluate its role in VEGF expression.

    • Main Results:

    • VEGF rapidly induces STAT3 tyrosine phosphorylation and nuclear translocation specifically in BREC.
    • VEGF forms a complex with VEGFR2 exclusively in BREC, not in aortic macrovascular endothelial cells (BAEC).
    • VEGF-induced VEGF mRNA expression is significantly increased in BREC, an effect diminished by STAT3 reduction.
    • Similar STAT3 activation and autocrine VEGF expression observed in human dermal microvascular endothelial cells (HDMEC).

    Conclusions:

    • VEGF differentially induces STAT3 activation in microvascular endothelial cells compared to macrovascular cells.
    • VEGFR2/STAT3 complex formation is crucial for VEGF-induced STAT3 activation in microvascular cells.
    • This pathway correlates with VEGF's autocrine ability to stimulate its own gene expression, highlighting a key mechanism in microvascular angiogenesis.