Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response

Anna I. Markowska, Fu-Tong Liu, Noorjahan Panjwani

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

Recent studies have shown that a carbohydrate-binding protein, galectin-3, is a novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate here that galectin-3 is a mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-mediated angiogenic response. Angiogenesis assays revealed that galectin-3 inhibitors, β-lactose and dominant-negative galectin-3, reduce VEGF- and bFGF-mediated angiogenesis in vitro and that VEGF- and bFGF-mediated angiogenic response is reduced in galectin-3 knockdown cells and Gal3 -/- animals. Integrin αvβ3 was identified as the major galectin-3-binding protein and anti-αv, -β3, and -αvβ3 integrin function-blocking antibodies significantly inhibited the galectin-3-induced angiogenesis. Furthermore, galectin-3 promoted the clustering of integrin αvβ3 and activated focal adhesion kinase. Knockdown of GnTV, an enzyme that synthesizes high-affinity glycan ligands for galectin-3, substantially reduced: (a) complex N-glycans on αvβ3 integrins and (b) VEGF- and bFGF-mediated angiogenesis. Collectively, these data suggest that galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding via its carbohydrate recognition domain, to the GnTV synthesized N-glycans of integrin αvβ3, and subsequently activating the signaling pathways that promote the growth of new blood vessels. These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis.

Original languageEnglish (US)
Pages (from-to)1981-1993
Number of pages13
JournalJournal of Experimental Medicine
Volume207
Issue number9
DOIs
StatePublished - Aug 30 2010

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Galectin 3
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Integrins
Polysaccharides
Carbohydrates
Focal Adhesion Protein-Tyrosine Kinases
Blocking Antibodies
Lactose
Blood Vessels
Cluster Analysis
Carrier Proteins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response. / Markowska, Anna I.; Liu, Fu-Tong; Panjwani, Noorjahan.

In: Journal of Experimental Medicine, Vol. 207, No. 9, 30.08.2010, p. 1981-1993.

Research output: Contribution to journalArticle

Markowska, Anna I. ; Liu, Fu-Tong ; Panjwani, Noorjahan. / Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response. In: Journal of Experimental Medicine. 2010 ; Vol. 207, No. 9. pp. 1981-1993.
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