Differentially expressed epigenome modifiers, including aurora kinases A and B, in immune cells in rheumatoid arthritis in humans and mouse models.
Differentially expressed epigenome modifiers, including aurora kinases A and B, in immune cells in rheumatoid arthritis in humans and mouse models.
复制标题
在人类和小鼠模型中，在类风湿关节炎中的免疫细胞中，差异表达的表观基因组修饰剂，包括Aurora激酶A和B。
DOI：
10.1002/art.37986
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发表时间：
2013-07
影响因子：
--
通讯作者：
Rauch, Tibor A.
中科院分区：
文献类型：
--
作者：
Glant, Tibor T.;Besenyei, Timea;Kadar, Andras;Kurko, Julia;Tryniszewska, Beata;Gal, Janos;Soos, Gyoergyi;Szekanecz, Zoltan;Hoffmann, Gyula;Block, Joel A.;Katz, Robert S.;Mikecz, Katalin;Rauch, Tibor A.
本研究的目的是确定与类风湿性关节炎（RA）发病机制有关的表观遗传因素，并探索靶向抑制这些因素的治疗潜力。 PCR 阵列用于研究编码关键表观遗传调节酶的基因的表达谱。监测来自 RA 患者和小鼠的单核细胞的基因表达变化，这些变化与 RA 小鼠模型中关节炎的发展相关。通过实时定量 PCR、蛋白质印迹和流式细胞术方法进一步表征所选基因。在关节炎小鼠中研究了上调酶的靶向抑制。 PCR 阵列鉴定出一组具有关节炎特异性表达的基因。极光激酶 A 和 B 在关节炎小鼠和未接受治疗的 RA 患者中高度表达，被选择进行详细分析。极光激酶表达升高伴随着组蛋白 H3 磷酸化的增加，从而促进 T 淋巴细胞的增殖。使用泛极光激酶抑制剂 VX-680 治疗可促进 B 细胞凋亡，提供显着的预防作用，并减轻关节炎小鼠的炎症反应。关节炎的发展伴随着许多表观基因组修饰酶表达的变化。除其他靶标外，药物诱导的极光激酶下调似乎足以治疗实验性关节炎。开发针对 Aurora 激酶的新疗法可能会改善 RA 的治疗。
The aim of this study was to identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA) and to explore the therapeutic potential of the targeted inhibition of these factors. PCR arrays were utilized to investigate the expression profile of genes that encod key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA. Selected genes were further characterized by quantitative real-time PCR, Western blot and flow cytometry methods. The targeted inhibition of the upregulated enzymes was studied in arthritic mice. A set of genes with arthritis-specific expression was identified by the PCR arrays. Aurora kinase A and B, both of which were highly expressed in arthritic mice and treatment naïve RA patients, were selected for detailed analysis. Elevated Aurora kinase expression was accompanied with an increased phosphorylation of histone H3, which promotes proliferation of T lymphocytes. Treatment with VX-680, a pan-Aurora kinase inhibitor, promoted B cell apoptosis, provided significant protection against the onset, and attenuated the inflammatory reactions in arthritic mice. Arthritis development is accompanied the changes in the expression of a number of epigenome-modifying enzymes. Drug-induced downregulation of the Aurora kinases, among other targets, seems to be sufficient to treat experimental arthritis. Development of new therapeutics that target the Aurora kinases can potentially improve RA management.
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影响因子：
7.5
作者：
Carmena M;Ruchaud S;Earnshaw WC
通讯作者：
Earnshaw WC
影响因子：
11.4
作者：
Beck, Ilse Me;Vanden Berghe, Wim;De Bosscher, Karolien
通讯作者：
De Bosscher, Karolien
影响因子：
5.7
作者：
Dar AA;Goff LW;Majid S;Berlin J;El-Rifai W
通讯作者：
El-Rifai W
影响因子：
4.9
作者：
Angyal, Adrienn;Egelston, Colt;Mikecz, Katalin
通讯作者：
Mikecz, Katalin
影响因子：
4.4
作者：
Adarichev, VA;Valdez, JC;Glant, TT
通讯作者：
Glant, TT