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N. A. Panjwani, F.-T. Liu, A. I. Markowska; Galectin-3 Is an Important Mediator of VEGF- and bFGF-Mediated Angiogenic Response. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4307.
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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 role of a carbohydrate-binding protein, galectin-3, in VEGF- and bFGF-mediated angiogenesis.
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 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.
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. 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.
Galectin-3 modulates VEGF- and bFGF-mediated angiogenic response. Possible mechanisms by which galectin-3 may modulate growth factor-induced angiogenesis include cross-linking VEGF and bFGF receptors and promoting crosstalk between the growth factor receptors and proangiogenic integrins. Galectin-3 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.
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