Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.
Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.
复制标题
蛋白精氨酸甲基转移酶5在类风湿性关节炎成纤维样滑膜细胞炎症和迁移中的作用
DOI：
10.1111/jcmm.13020
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发表时间：
2017-04
影响因子：
5.3
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Chen D;Zeng S;Huang M;Xu H;Liang L;Yang X
探讨蛋白质精氨酸甲基转移酶5（PRMT 5）在类风湿关节炎（RA）患者成纤维样滑膜细胞（FLS）炎症、细胞增殖、迁移和侵袭中的作用。从RA和骨关节炎（OA）患者的滑膜组织（ST）中分离FLS。使用PRMT 5的抑制剂（EPZ 015666）和针对PRMT 5的短干扰RNA（siRNA）来抑制PRMT 5表达。蛋白质标准品用Western blot或免疫荧光法测定。分别通过酶联免疫吸附试验（ELISA）和真实的实时聚合酶链反应（PCR）估计炎症因子的排泄和基因表达。Boyden小室法检测细胞的体外迁移和侵袭能力。BrdU掺入法检测FLS增殖。PRMT 5在RA患者的ST和FLS中增加。在RA FLS中，PRMT 5的水平通过IL-1β和TNF-α刺激而上调。EPZ 015666和siRNA介导的敲低对PRMT 5的抑制减少了IL-6和IL-8的产生以及RA FLS的增殖。此外，PRMT 5的抑制降低了RA FLS的体外迁移和侵袭。EPZ 0 15 6 6 6抑制FLS中IκB激酶β和IκBα的磷酸化以及p6 5和AKT的核转位。PRMT 5通过NF-κB和AKT通路调节RA FLS的炎症因子产生、细胞增殖、迁移和侵袭。我们的数据表明，靶向PRMT 5以防止滑膜炎症和破坏可能是RA的一种有希望的治疗方法。
To probe the role of protein arginine methyltransferase 5 (PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast‐like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). FLSs were separated from synovial tissues (STs) from patients with RA and osteoarthritis (OA). An inhibitor of PRMT5 (EPZ015666) and short interference RNA (siRNA) against PRMT5 were used to inhibit PRMT5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme‐linked immunosorbent assay (ELISA) and real‐time polymerase chain reaction (PCR). Migration and invasion in vitro were detected by Boyden chamber assay. FLSs proliferation was detected by BrdU incorporation. Increased PRMT5 was discovered in STs and FLSs from patients with RA. In RA FLSs, the level of PRMT5 was up‐regulated by stimulation with IL‐1β and TNF‐α. Inhibition of PRMT5 by EPZ015666 and siRNA‐mediated knockdown reduced IL‐6 and IL‐8 production, and proliferation of RA FLSs. In addition, inhibition of PRMT5 decreased in vitro migration and invasion of RA FLSs. Furthermore, EPZ015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLSs. PRMT5 regulated the production of inflammatory factors, cell proliferation, migration and invasion of RA FLS, which was mediated by the NF‐κB and AKT pathways. Our data suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA.