April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Galectin-3 Influences VEGF- and bFGF-Mediated Angiogenesis by Modulating the Activity of vβ3 Integrin
Author Affiliations & Notes
  • A. Markowska
    Departments of Ophthalmology and Biochemistry, Tufts University, Boston, Massachusetts
  • F.-T. Liu
    Department of Dermatology, University of California Davis School of Medicine, Davis, California
  • N. Panjwani
    Departments of Ophthalmology and Biochemistry, Tufts University, Boston, Massachusetts
    New England Eye Center, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  A. Markowska, None; F.-T. Liu, None; N. Panjwani, None.
  • Footnotes
    Support  NIH: EY007088 (NP), R01AI20958 (FTL); New England Corneal Transplant Fund, Mass Lions Eye Research Fund, Research to Prevent Blindness Grant, Consortium for Functional Glycomics (GM62116).
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2036. doi:https://doi.org/
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      A. Markowska, F.-T. Liu, N. Panjwani; Galectin-3 Influences VEGF- and bFGF-Mediated Angiogenesis by Modulating the Activity of vβ3 Integrin. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2036. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Angiogenesis is a key factor in the pathogenesis of a number of ocular diseases including corneal graft failure, age-related macular degeneration and diabetic retinopathy. In this study, we investigate the mechanism of a carbohydrate-binding protein, galectin-3, in VEGF- and bFGF-mediated angiogenesis

Methods: : Capillary tubule formation assays and cell migration assays were performed using HUVECs in which expression of galectin-3 and GnTV were knocked-down to evaluate the significance of galectin-3 in VEGF- and bFGF-mediated angiogenesis in vitro. Experiments were also performed in the presence of integrin blocking antibodies, saccharide inhibitors of galectins and dominant negative galectin-3. Mouse corneal micropocket assays were performed in GnTV-/-, GnTV+/+, Gal3-/- and Gal3+/+ to evaluate angiogenesis in vivo.

Results: : Saccharide inhibitors of galectin-3 as well as dominant negative galectin-3 significantly reduced VEGF- and bFGF-mediated angiogenesis in vitro. VEGF- and bFGF-mediated angiogenic response was also reduced in galectin-3 knockdown HUVECs and in Gal3-/- animals as compared to the wild type mice. Integrin αvβ3, a critical component of the VEGF and bFGF angiogenic cascade, was identified as the major galectin-3-binding protein in human umbilical vein endothelial cells (HUVECs) and anti-αv, -β3 as well as -αvβ3 integrin function-blocking antibodies significantly inhibited the galectin-3-induced angiogenesis. Furthermore, galectin-3 promoted clustering of integrin αvβ3 and activated focal adhesion kinase (FAK). Disruption of GnTV, an enzyme which synthesizes high affinity glycan ligands for galectin-3, diminished VEGF- and bFGF-mediated angiogenesis in vitro. Furthermore, VEGF- and bFGF-mediated angiogenesis was reduced in GnTV-/- animals as compared to the wild type mice.

Conclusions: : Galectin-3 influences VEGF- and bFGF-mediated angiogenic response by modulating the function of integrin αvβ3 and as such may serve as a valuable target for effective angiogenesis inhibition in a number of devastating clinical conditions including corneal graft failure, age- related macular degeneration and diabetic retinopathy.

Keywords: neovascularization 
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