Literature DB >> 24665114

A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K/BxN arthritis.

Mohammad A Amin1, Phillip L Campbell1, Jeffrey H Ruth1, Takeo Isozaki1, Bradley J Rabquer1, W Alex Stinson1, Martin O'Brien1, Gautam Edhayan1, Ray A Ohara1, Jonathon Vargo1, Steven E Domino2, Alisa E Koch3.   

Abstract

OBJECTIVES: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Entities:  

Keywords:  Arthritis; Inflammation; Rheumatoid Arthritis

Mesh:

Substances:

Year:  2014        PMID: 24665114     DOI: 10.1136/annrheumdis-2013-204814

Source DB:  PubMed          Journal:  Ann Rheum Dis        ISSN: 0003-4967            Impact factor:   19.103


  7 in total

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Authors:  Pei-Suen Tsou; Chenyang Lu; Mikel Gurrea-Rubio; Sei Muraoka; Phillip L Campbell; Qi Wu; Ellen N Model; Matthew E Lind; Sirapa Vichaikul; Megan N Mattichak; William D Brodie; Jonatan L Hervoso; Sarah Ory; Camila I Amarista; Rida Pervez; Lucas Junginger; Mustafa Ali; Gal Hodish; Morgan M O'Mara; Jeffrey H Ruth; Aaron M Robida; Andrew J Alt; Chengxin Zhang; Andrew G Urquhart; Jeffrey N Lawton; Kevin C Chung; Tristan Maerz; Thomas L Saunders; Vincent E Groppi; David A Fox; M Asif Amin
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Authors:  Huan-Hsien Kuo; Ruey-Jen Lin; Jung-Tung Hung; Chung-Bao Hsieh; Tsai-Hsien Hung; Fei-Yun Lo; Ming-Yi Ho; Chau-Ting Yeh; Yen-Lin Huang; John Yu; Alice L Yu
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  7 in total

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