Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis.
Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis.
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岩藻糖基转移酶1介导类风湿关节炎中的血管生成。
DOI：
10.1002/art.38648
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发表时间：
2014-08
影响因子：
13.3
通讯作者：
Koch, Alisa E.
中科院分区：
文献类型：
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作者：
Isozaki, Takeo;Amin, Mohammad A.;Ruth, Jeffrey H.;Campbell, Phillip L.;Tsou, Pei-Suen;Ha, Christine M.;Stinson, W. Alex;Domino, Steven E.;Koch, Alisa E.
本研究的目的是确定岩藻糖基转移酶1（fut 1）α（1，2）-连接的岩藻糖基化蛋白质在类风湿关节炎（RA）血管生成中的作用。通过免疫组织化学染色分析滑膜组织（ST）中的α（1，2）-连接岩藻糖基化蛋白。用免疫沉淀法和凝集素印迹法测定关节滑液中α（1，2）-岩藻糖基化血管生成趋化因子的表达。为了确定α（1，2）-连接岩藻糖基化蛋白在RA中的血管生成作用，我们使用非耗尽和α（1，2）-连接岩藻糖基化蛋白耗尽的RA SF进行人真皮微血管内皮细胞（HMVEC）趋化性和基质胶测定。为了检测岩藻糖基转移酶1（fut 1）在HMVECs中促血管生成趋化因子的产生，用fut 1正义或反义寡核苷酸转染细胞，并进行酶联免疫吸附测定。然后，我们研究了小鼠肺内皮细胞（MLEC）的趋化性使用野生型和fut 1基因缺陷MLEC。与正常ST相比，RA ST内皮细胞（EC）上的α（1，2）-连接岩藻糖基化蛋白高度表达。RA SF中存在α（1，2）-连接岩藻糖基化单核细胞趋化蛋白-1（MCP-1）/CCL 2，并且与骨关节炎SF相比显著升高。与未耗竭的RA SF相比，RA SF中α（1，2）-连接岩藻糖基化蛋白的耗竭诱导较少的HMVEC迁移和管形成。我们发现，阻断内皮细胞中的fut 1表达导致MCP-1/CCL 2降低，并调节活化和正常T细胞表达和分泌（RANTES）/CCL 5的产生。最后，我们发现，fut 1调节EC迁移响应血管内皮细胞生长因子。fut 1的α（1，2）-连接岩藻糖基化可能是RA等血管生成性疾病的重要新靶点。
The aim of this study was to determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase1 (fut1) in rheumatoid arthritis (RA) angiogenesis. Analysis of α(1,2)-linked fucosylated proteins in synovial tissues (STs) was performed by immunohistological staining. α(1,2)-linked fucosylated angiogenic chemokine expression in synovial fluids (SFs) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using nondepleted and α(1,2)-linked fucosylated protein depleted RA SFs. To examine the production of proangiogenic chemokines by fucosyltransferase 1 (fut1) in HMVECs, cells were transfected with fut1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (MLEC) chemotaxis using wild type and fut1 gene deficient MLECs. α(1,2)-linked fucosylated proteins on RA ST endothelial cells (ECs) were highly expressed compared to normal ST. α(1,2)-linked fucosylated monocyte chemoattract protein-1 (MCP-1)/CCL2 was present in RA SFs, and was significantly elevated compared to osteoarthritis SFs. Depletion of α(1,2)-linked fucosylated proteins in RA SFs induced less HMVEC migration and tube formation compared to nondepleted RA SFs. We found that blocking fut1 expression in ECs resulted in decreased MCP-1/CCL2 and regulated upon activation and normal T cell expressed and secreted (RANTES)/CCL5 production. Finally, we showed that fut1 regulates EC migration in response to vascular endothelial cell growth factor. α(1,2)-linked fucosylation by fut1 may be an important new target for angiogenic diseases like RA.
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影响因子：
7.3
作者：
MACARTNEY, JC
通讯作者：
MACARTNEY, JC
影响因子：
--
作者：
Marotte, Hubert;Tsou, Pei-Suen;Koch, Alisa E.
通讯作者：
Koch, Alisa E.
影响因子：
4.3
作者：
Fukushima, Keiko;Satoh, Takefumi;Yamashita, Katsuko
通讯作者：
Yamashita, Katsuko
DOI：
10.1073/pnas.87.17.6674
发表时间：
1990-09-01
影响因子：
11.1
作者：
LARSEN, RD;ERNST, LK;LOWE, JB
通讯作者：
LOWE, JB
影响因子：
64.8
作者：
KOCH, AE;HALLORAN, MM;POLVERINI, PJ
通讯作者：
POLVERINI, PJ