title: Identification of galectin-1 and galectin-3 as novel partners for von Willebrand factor.
abstract: OBJECTIVE
  Although von Willebrand factor (VWF) is a heavily glycosylated protein, its potential to associate with glycan-binding proteins is poorly investigated. Here, we explored its interaction with the glycan-binding proteins galectin-1 and galectin-3.
  
  
  RESULTS
  Immunofluorescence analysis using Duolink proximity ligation assays revealed that VWF colocalizes with galectin-1 and galectin-3 in endothelial cells, both before and after stimulation of endothelial cells. Moreover, galectin-1 was found along the typical VWF bundles that are released by endothelial cells. Galectin-1 and galectin-3 could be coprecipitated with VWF from plasma in immunoprecipitation assays, whereas plasma levels of galectin-1 and galectin-3 were significantly reduced in VWF-deficient mice. Binding studies using purified proteins confirmed that VWF could directly interact with both galectins, predominantly via its N-linked glycans. In search of the physiological relevance of the VWF-galectin interaction, we found that inhibition of galectins in in vitro perfusion assays was associated with increased VWF-platelet string formation, a phenomenon that was reproduced in galectin-1/galectin-3 double-deficient mice. These mice were also characterized by a more rapid formation of initial thrombi following ferric chloride-induced injury.
  
  
  CONCLUSIONS
  We have identified galectin-1 and galectin-3 as novel partners for VWF, and these proteins may modulate VWF-mediated thrombus formation.
authors.affiliation: INSERM U, Le Kremlin-Bicêtre, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saint-Lu
authors.forename: Beatrijs D
authors.initials: BD
authors.lastname: Oortwijn
authors.forename: Julie N
authors.initials: JN
authors.lastname: Pegon
authors.forename: Soline
authors.initials: S
authors.lastname: Odouard
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Christophe
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Cécile V
authors.initials: CV
authors.lastname: Denis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides; D004195:Disease Models, Animal; D005290:Ferric Compounds; D037483:Galectin 1 / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D037502:Galectin 3 / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010973:Platelet Adhesiveness; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D013997:Time Factors; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D037483:Galectin 1; D037502:Galectin 3; C445499:LGALS1 protein, human; C485095:Lgals3 protein, mouse; D014841:von Willebrand Factor; C024555:ferric chloride