Protein tyrosine phosphatase expression profile of rheumatoid arthritis fibroblast-like synoviocytes: a novel role of SH2 domain-containing phosphatase 2 as a modulator of invasion and survival.
Protein tyrosine phosphatase expression profile of rheumatoid arthritis fibroblast-like synoviocytes: a novel role of SH2 domain-containing phosphatase 2 as a modulator of invasion and survival.
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DOI：
10.1002/art.37872
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发表时间：
2013-05
影响因子：
--
通讯作者：
Bottini, Nunzio
中科院分区：
文献类型：
--
作者：
Stanford, Stephanie M.;Maestre, Michael F.;Campbell, Amanda M.;Bartok, Beatrix;Kiosses, William B.;Boyle, David L.;Arnett, Heather A.;Mustelin, Tomas;Firestein, Gary S.;Bottini, Nunzio
类风湿关节炎（RA）滑膜内膜中的成纤维细胞样滑膜细胞（FLS）是炎症和关节破坏的关键介质。在RA中，这些细胞侵袭细胞外基质，产生软骨降解蛋白酶和炎性细胞因子。FLS的行为是由多个相互关联的信号转导途径控制的，包括酪氨酸残基上蛋白质的可逆磷酸化。然而，很少有人知道蛋白酪氨酸磷酸酶（PTPs）在FLS功能中的作用。本研究的目的是探讨所有PTP基因（PTPome）在FLS中的表达。对来自RA或骨关节炎（OA）患者的FLS中PTPome的表达进行比较筛选。然后通过在RA FLS中使用细胞可渗透的反义寡核苷酸敲低来分析在RA中上调的PTP SHP-2的功能效应。与OA FLS相比，PTPN 11在RA中过表达。使用可渗透细胞的反义寡核苷酸敲除编码SHP-2的PTPN 11，可降低RA FLS的侵袭、迁移、粘附、扩散和存活。此外，响应于生长因子和炎性细胞因子的信号传导通过SHP-2的敲低而受损。SHP-2缺陷的RA FLS显示粘着斑激酶和丝裂原活化蛋白激酶的活化降低。这些发现表明SHP-2在介导人类FLS功能中的新作用，并表明SHP-2促进RA FLS的侵袭性和存活。进一步的研究可能揭示SHP-2是RA的候选治疗靶点。
The fibroblast-like synoviocytes (FLS) in the synovial intimal lining of the joint are key mediators of inflammation and joint destruction in rheumatoid arthritis (RA). In RA, these cells aggressively invade the extracellular matrix, producing cartilage-degrading proteases and inflammatory cytokines. The behavior of FLS is controlled by multiple interconnected signal transduction pathways involving reversible phosphorylation of proteins on tyrosine residues. However, little is known about the role of the protein tyrosine phosphatases (PTPs) in FLS function. The objective of this study was to explore the expression of all the PTP genes (PTPome) in FLS. A comparative screening was conducted of the expression of the PTPome in FLS from patients with RA or osteoarthritis (OA). The functional effect of a PTP up-regulated in RA, SHP-2, was then analyzed by knock-down using cell-permeable antisense oligonucleotides in RA FLS. PTPN11 was over-expressed in RA compared to OA FLS. Knock-down of PTPN11, which encodes SHP-2, using a cell-permeable antisense oligonucleotide, decreased the invasion, migration, adhesion, spreading and survival of RA FLS. Additionally, signaling in response to growth factors and inflammatory cytokines was impaired by the knock-down of SHP-2. RA FLS deficient in SHP-2 displayed decreased activation of focal adhesion kinase and mitogen-activated protein kinases. These findings indicate a novel role for SHP-2 in mediating human FLS function, and suggest that SHP-2 promotes the invasiveness and survival of RA FLS. Further investigation may reveal SHP-2 to be a candidate therapeutic target for RA.
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影响因子：
5.5
作者：
Pattacini, Laura;Boiardi, Luigi;Salvarani, Carlo
通讯作者：
Salvarani, Carlo
DOI：
10.1186/ar109
发表时间：
2000
期刊：
Arthritis research
影响因子：
--
作者：
Kontoyiannis D;Kollias G
通讯作者：
Kollias G
影响因子：
2.7
作者：
Morcos, Paul A.;Li, Yongfu;Jiang, Shan
通讯作者：
Jiang, Shan
影响因子：
6
作者：
Hou, WS;Li, ZQ;Brömme, D
通讯作者：
Brömme, D
关节炎严重性基因座CIA5D是滑膜成纤维细胞侵入性特性的新型遗传调节剂。
影响因子：
--
作者：
Laragione, Teresina;Brenner, Max;Mello, Adriana;Symons, Marc;Gulko, Percio S.
通讯作者：
Gulko, Percio S.