Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues.
Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues.
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DOI：
10.1186/ar2318
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发表时间：
2007
影响因子：
4.9
通讯作者：
Koch AE
中科院分区：
文献类型：
--
作者：
Shahrara S;Castro-Rueda HP;Haines GK;Koch AE
局点粘附激酶（FAK）家族激酶，包括FAK和富含脯氨酸的激酶2 (Pyk)2，是整合素αvβ3信号事件的主要介质，在细胞粘附、破骨细胞病理和血管生成中起重要作用，这些过程在类风湿关节炎（RA）中都很重要。利用免疫组织化学和western blot分析，我们研究了磷酸(p)FAK、pPyk2、pSrc、pPaxillin和pPLCγ在RA、骨关节炎（OA）和正常供者（nd）滑膜组织（ST）中的分布，以及肿瘤坏死因子-α (TNFα)或白细胞介素-1β (il -1β)治疗的RA ST成纤维细胞和外周血分化巨噬细胞（PB MΦs）中的分布。与ND ST相比，RA和OA ST在衬里细胞和MΦs上显示出更高的pFAK百分比，RA ST成纤维细胞在基线时表达pFAK，随着TNFα或il - 1β的刺激而增加。与OA和ND衬里细胞和MΦs相比，Pyk2和Src在RA中磷酸化更多。pPyk2在RA ST纤维母细胞中表达，但在MΦs中不表达，但在两种细胞类型中，pPyk2在TNFα或il - 1β激活时均上调。pSrc在基线时在RA ST成纤维细胞和MΦs中表达，并在TNFα或il - 1β刺激下进一步升高。与OA和ND相比，paxillin和pPLCγ在RA中上调，并在MΦs中降低。FAK家族信号级联在RA和OA衬细胞上的激活可能是细胞粘附和迁移到病变STs的原因。针对这种新的信号通路的治疗可能对RA有益。
The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators of integrin αvβ3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution of phospho (p)FAK, pPyk2, pSrc, pPaxillin and pPLCγ in the synovial tissue (ST) from patients with RA, osteoarthritis (OA) and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB MΦs) treated with tumor necrosis factor-α (TNFα) or interleukin-1β (IL1β). RA and OA STs showed a greater percentage of pFAK on lining cells and MΦs compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNFα or IL1β stimulation. Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MΦs. pPyk2 was expressed on RA ST fibrobasts but not in MΦs at baseline, however it was upregulated upon TNFα or IL1β activation in both cell types. pSrc was expressed in RA ST fibroblasts and MΦs at baseline and was further increased by TNFα or IL1β stimulation. pPaxillin and pPLCγ were upregulated in RA versus OA and ND lining cells and sublining MΦs. Activation of the FAK family signaling cascade on RA and OA lining cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway may be beneficial in RA.
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影响因子：
64.8
作者：
HORWITZ, A;DUGGAN, K;BURRIDGE, K
通讯作者：
BURRIDGE, K
影响因子：
--
作者：
Nishikawa, M;Myoui, A;Yoshikawa, H
通讯作者：
Yoshikawa, H
DOI：
10.1083/jcb.152.2.361
发表时间：
2001-01-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nakamura I;Lipfert L;Rodan GA;Le T Duong
通讯作者：
Le T Duong
DOI：
10.1083/jcb.135.4.1109
发表时间：
1996-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Brown MC;Perrotta JA;Turner CE
通讯作者：
Turner CE
影响因子：
4.8
作者：
Chen, HC;Appeddu, PA;Guan, JL
通讯作者：
Guan, JL