title: Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase 1 (FUT1) in rheumatoid arthritis (RA) angiogenesis.
  
  
  METHODS
  Analysis of α(1,2)-linked fucosylated proteins in synovial tissue (ST) samples was performed by immunohistologic staining. Expression of α(1,2)-linked fucosylated angiogenic chemokine in synovial fluid (SF) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using sham-depleted and α(1,2)-linked fucosylated protein-depleted RA SF samples. To examine the production of proangiogenic chemokines by FUT1 in HMVECs, cells were transfected with FUT1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (EC) chemotaxis using wild-type and FUT1 gene-deficient mouse lung ECs.
  
  
  RESULTS
  RA ST endothelial cells showed high expression of α(1,2)-linked fucosylated proteins compared to normal ST. The expression of α(1,2)-linked fucosylated monocyte chemoattractant protein 1 (MCP-1)/CCL2 was significantly elevated in RA SF compared with osteoarthritis SF. Depletion of α(1,2)-linked fucosylated proteins in RA SF induced less HMVEC migration and tube formation than occurred in sham-depleted RA SF. We found that blocking FUT1 expression in ECs resulted in decreased MCP-1/CCL2 and RANTES/CCL5 production. Finally, we showed that FUT1 regulates EC migration in response to vascular endothelial cell growth factor.
  
  
  CONCLUSIONS
  Our findings indicate that α(1,2)-linked fucosylation by FUT1 may be an important new target for angiogenic diseases such as RA.
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Takeo
authors.initials: T
authors.lastname: Isozaki
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Amin
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ruth
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Campbell
authors.forename: Pei-Suen
authors.initials: PS
authors.lastname: Tsou
authors.forename: Christine M
authors.initials: CM
authors.lastname: Ha
authors.forename: W Alex
authors.initials: WA
authors.lastname: Stinson
authors.forename: Steven E
authors.initials: SE
authors.lastname: Domino
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D005647:Fucosyltransferases / Q000502:physiology*; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase