Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.
Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.
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DOI：
10.1371/journal.pone.0099607
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Pablos JL
中科院分区：
文献类型：
--
作者：
Del Rey MJ;Faré R;Izquierdo E;Usategui A;Rodríguez-Fernández JL;Suárez-Fueyo A;Cañete JD;Pablos JL
滑膜成纤维细胞（SF）在类风湿性关节炎（RA）中发生表型变化，导致炎性关节破坏。本研究旨在评价RA SF异位表达podoplanin（gp 38）的临床和功能意义。通过免疫组织化学方法分析RA患者、正常人和骨关节炎对照的滑膜关节镜活检组织中gp 38及其CLEC 2受体的表达。分析gp 38表达与RA临床病理变量的相关性。在抗TNF-α治疗后再次活检的患者中，测定gp 38表达的变化。血小板-SF共培养和SF中的gp 38沉默被用于分析gp 38对SF迁移和侵袭性质以及对SF血小板串扰的功能贡献。gp 38在RA中表达丰富，但表达量较少，在正常滑膜组织中未见表达。在临床病理RA变量中，仅在淋巴新生（LN）和RF或ACPA自身抗体患者中发现gp 38表达显著增加。培养的滑膜成纤维细胞而非真皮成纤维细胞显示出强烈的组成型gp 38表达，其进一步被TNF-α诱导。在RA患者中，抗TNF-α治疗显著降低滑膜gp 38表达。在RA滑膜中，CLEC 2受体表达仅在血小板中观察到。培养SF中gp 38沉默并没有改变其迁移和侵袭特性，但降低了SF-血小板相互作用诱导的IL-6和IL-8基因的表达。在RA中，滑膜gp 38的表达与LN密切相关，并且在抗TNF-α治疗后减少。gp 38和CLEC 2血小板受体之间的相互作用在体内RA滑膜中是可行的，并且可以特异性地促进SF的基因表达。
Synovial fibroblasts (SF) undergo phenotypic changes in rheumatoid arthritis (RA) that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38) expression by RA SF. Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk. gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN), and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction. In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.
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肿瘤坏死因子α诱导持续的信号传导，并在类风湿关节炎滑膜成纤维细胞中延长且不舒服的炎症反应。
影响因子：
--
作者：
Lee A;Qiao Y;Grigoriev G;Chen J;Park-Min KH;Park SH;Ivashkiv LB;Kalliolias GD
通讯作者：
Kalliolias GD
影响因子：
20.3
作者：
Bertozzi, Cara C.;Schmaier, Alec A.;Kahn, Mark L.
通讯作者：
Kahn, Mark L.
影响因子：
3.9
作者：
Genovese, Mark C.;Rubbert-Roth, Andrea;Van Vollenhoven, Ronald
通讯作者：
Van Vollenhoven, Ronald
DOI：
10.1152/ajplung.00171.2010
发表时间：
2011-01-01
影响因子：
4.9
作者：
Navarro, Angels;Perez, Ricardo E.;Ekekezie, Ikechukwu I.
通讯作者：
Ekekezie, Ikechukwu I.
影响因子：
--
作者：
Bradfield, PF;Amft, N;Buckley, CD
通讯作者：
Buckley, CD