Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation

• Published in: Arthritis research & therapy 2014-01, Vol.16 (1), p.R28-R28, Article R28
• Main Authors: Isozaki, Takeo, Ruth, Jeffrey H, Amin, Mohammad A, Campbell, Phillip L, Tsou, Pei-Suen, Ha, Christine M, Haines, G Kenneth, Edhayan, Gautam, Koch, Alisa E
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Cell Adhesion - physiology; Cell Proliferation; Cells, Cultured; Endothelium; Enzyme-Linked Immunosorbent Assay; Fibroblasts - metabolism; Fibroblasts - pathology; Fluorescent Antibody Technique; Fucosyltransferases - metabolism; Galactoside 2-alpha-L-fucosyltransferase; Humans; Immunity; Immunohistochemistry; Neovascularization, Pathologic - metabolism; Physiological aspects; Reverse Transcriptase Polymerase Chain Reaction; Synovial Membrane - metabolism; Transfection; Up-Regulation
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/ar4456

We previously reported that sialyl Lewis(y), synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewis(y) antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined. Assay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed. Total α(1,2)-linked fucosylated proteins in RA ST were significantly higher compared to normal (NL) ST. Fut1 expression on RA ST lining cells positively correlated with ST inflammation. HMVECs from a co-culture system with fut1 siRNA transfected RA synovial fibroblasts exhibited decreased endothelial cell tube formation compared to control siRNA transfected RA synovial fibroblasts. Fut1 siRNA also inhibited myeloid THP-1 adhesion to RA synovial fibroblasts and RA synovial fibroblast proliferation. These data show that α(1,2)-linked fucosylated proteins are upregulated in RA ST compared to NL ST. We also show that fut1 in RA synovial fibroblasts is important in angiogenesis, leukocyte-synovial fibroblast adhesion, and synovial fibroblast proliferation, all key processes in the pathogenesis of RA.