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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Nuclear factor kappaB dependency of platelet-activating factor-induced angiogenesis
Hyun-Mi Ko1, Kook Heon Seo, Su-Ji Han
1Department of Biological Sciences, The Institute of Basic Sciences, Research Institute of Medical Science, Chonnam National University, Kwangju 500-757, Japan.
Cancer Research
|March 26, 2002
Summary
Platelet-activating factor (PAF) promotes new blood vessel growth (angiogenesis) by activating nuclear factor kappa B (NFκB). This pathway is crucial for PAF-driven angiogenesis, particularly involving vascular endothelial growth factor (VEGF).
Area of Science:
- Molecular Biology
- Immunology
- Angiogenesis Research
Background:
- Platelet-activating factor (PAF) is implicated in various biological processes, including inflammation and immune responses.
- Angiogenesis, the formation of new blood vessels, is a critical process in development, wound healing, and disease pathology.
Purpose of the Study:
- To elucidate the molecular mechanisms by which PAF induces angiogenesis.
- To investigate the role of nuclear factor kappa B (NFκB) and downstream angiogenic factors in PAF-mediated angiogenesis.
Main Methods:
- Utilized a mouse Matrigel implantation model to assess angiogenesis.
- Employed NFκB inhibitors (p65 antisense) and antioxidants (alpha-tocopherol, N-acetyl-L-cysteine) to block signaling pathways.
- Analyzed mRNA and protein expression of angiogenic factors in human umbilical vein endothelial cells.
- Investigated the effects of blocking specific angiogenic factors (VEGF, TNF-α, IL-1α, bFGF) using antibodies and soluble receptors.
Main Results:
- PAF demonstrated a dose- and time-dependent induction of angiogenesis in vivo.
- Inhibition of NFκB activation or antioxidant treatment significantly attenuated PAF-induced angiogenesis.
- PAF stimulated the expression of NFκB-dependent angiogenic factors, including VEGF, in endothelial cells.
- Blocking VEGF, but not other tested factors, effectively inhibited the angiogenic effects of PAF.
Conclusions:
- PAF enhances angiogenesis primarily through the activation of the NFκB signaling pathway.
- NFκB activation leads to the increased production of key angiogenic factors, notably VEGF.
- VEGF plays a critical role in mediating the pro-angiogenic effects of PAF.
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