In:
Annals of the Rheumatic Diseases, BMJ, Vol. 74, No. 7 ( 2015-07), p. 1459-1466
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2013-204814
Language:
English
Publisher:
BMJ
Publication Date:
2015
detail.hit.zdb_id:
1481557-6
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