title: A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K/BxN arthritis.
abstract: OBJECTIVE
  Angiogenesis contributes to the pathogenesis of rheumatoid arthritis. Fucosyltransferases (Futs) are involved in angiogenesis and tumour growth. Here, we examined the role of Fut1 in angiogenesis and K/BxN serum transfer arthritis.
  
  
  METHODS
  We examined Fut1 expression in human dermal microvascular endothelial cells (HMVECs) by quantitative PCR. We performed a number of angiogenesis assays to determine the role of Fut1 using HMVECs, Fut1 null (Fut1(-/-)), and wild type (wt) endothelial cells (ECs) and mice. K/BxN serum transfer arthritis was performed to determine the contribution of Fut1-mediated angiogenesis in Fut1(-/-) and wt mice. A static adhesion assay was implemented with RAW264.7 (mouse macrophage cell line) and mouse ECs. Quantitative PCR, immunofluorescence and flow cytometry were performed with Fut1(-/-) and wt ECs for adhesion molecule expression.
  
  
  RESULTS
  Tumour necrosis factor-α induced Fut1 mRNA and protein expression in HMVECs. HMVECs transfected with Fut1 antisense oligodeoxynucleotide and Fut1(-/-) ECs formed significantly fewer tubes on Matrigel. Fut1(-/-) mice had reduced angiogenesis in Matrigel plug and sponge granuloma angiogenesis assays compared with wt mice. Fut1(-/-) mice were resistant to K/BxN serum transfer arthritis and had decreased angiogenesis and leucocyte ingress into inflamed joints. Adhesion of RAW264.7 cells to wt mouse ECs was significantly reduced when Fut1 was lacking. Fut1(-/-) ECs had decreased intercellular adhesion molecule-1 (ICAM-1) expression at mRNA and protein levels compared with wt ECs. ICAM-1 was also decreased in Fut1(-/-) arthritic ankle cryosections compared with wt ankles.
  
  
  CONCLUSIONS
  Fut1 plays an important role in regulating angiogenesis and ICAM-1 expression in inflammatory arthritis.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Amin
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Campbell
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ruth
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Takeo
authors.initials: T
authors.lastname: Isozaki
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Rabquer
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: W
authors.initials: W
authors.lastname: Alex Stinson
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: O'Brien
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Edhayan
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Ray A
authors.initials: RA
authors.lastname: Ohara
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Vargo
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Domino
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA Veteran's Administration, Ann Arbor, Michigan, USA.
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D018799:Intercellular Adhesion Molecule-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: Arthritis; Inflammation; Rheumatoid Arthritis