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Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

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Computational gene network analysis reveals TNF-induced angiogenesis.

Kentaro Ogami1, Rui Yamaguchi, Seiya Imoto

  • 1Human Genome Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan.

BMC Systems Biology
|January 4, 2013
PubMed
Summary

Tumor Necrosis Factor-α (TNF) promotes blood vessel formation, crucial in cancer and rheumatic diseases. A novel gene network involving IL6 and IL8 was identified, inhibiting apoptosis and driving TNF-induced angiogenesis.

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Cancer Research

Background:

  • Tumor Necrosis Factor-alpha (TNF) stimulates Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and angiogenesis.
  • TNF-induced angiogenesis is implicated in cancer and rheumatic diseases.
  • The underlying molecular mechanisms of TNF-induced angiogenesis remain largely unelucidated.

Purpose of the Study:

  • To elucidate the molecular system driving TNF-induced angiogenesis.
  • To identify key genes and pathways involved in TNF-stimulated HUVEC responses.

Main Methods:

  • Gene expression analysis of TNF-stimulated HUVECs using microarrays over a time course.
  • K-means clustering and functional enrichment analysis (DAVID) to identify gene patterns.
  • Bayesian network and nonparametric regression for gene network construction.
  • Integration of biological knowledge to identify angiogenesis-related sub-networks.

Main Results:

  • Identified three biologically informative gene expression clusters related to apoptosis, cellular proliferation, and angiogenesis.
  • Constructed dynamic Bayesian networks from 648 identified genes.
  • Hypothesized a sub-network including IL6 and IL8 that inhibits apoptosis and promotes TNF-induced angiogenesis.
  • IL6 was found to promote angiogenesis by inducing NF-κB and IL8, potent cell growth factors.

Conclusions:

  • Computational gene network analysis revealed a novel molecular system critical for TNF-induced angiogenesis.
  • The findings offer insights into the pathogenesis of cancer and rheumatic diseases.
  • Bayesian network analysis combined with functional annotation is a powerful approach for disease mechanism discovery.