Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation
dc.contributor.author | Isozaki, Takeo | |
dc.contributor.author | Ruth, Jeffrey H | |
dc.contributor.author | Amin, Mohammad A | |
dc.contributor.author | Campbell, Phillip L | |
dc.contributor.author | Tsou, Pei-Suen | |
dc.contributor.author | Ha, Christine M | |
dc.contributor.author | Haines, G K | |
dc.contributor.author | Edhayan, Gautam | |
dc.contributor.author | Koch, Alisa E | |
dc.date.accessioned | 2014-12-08T17:46:24Z | |
dc.date.available | 2014-12-08T17:46:24Z | |
dc.date.issued | 2014-01-28 | |
dc.identifier.citation | Arthritis Research & Therapy. 2014 Jan 28;16(1):R28 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/109505 | en_US |
dc.description.abstract | Abstract Introduction We previously reported that sialyl Lewisy, 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 Lewisy antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined. Methods 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. Results 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. Conclusions 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. | |
dc.title | Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/109505/1/13075_2012_Article_4111.pdf | |
dc.identifier.doi | 10.1186/ar4456 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Isozaki et al.; licensee BioMed Central Ltd. | |
dc.date.updated | 2014-12-08T17:46:24Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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