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TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis.
European Cytokine Network ( IF 2.8 ) Pub Date : 2018-05-18 , DOI: 10.1684/ecn.2018.0405
Mahmoud Al-Azab 1 , Jing Wei 1 , Xunli Ouyang 1 , Abdalkhalig Elkhider 1 , Williams Walana 1 , Xiaotong Sun 1 , Yawei Tang 1 , Bing Wang 1 , Xia Li 1
Affiliation  

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2).We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients’ samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.

中文翻译:

TL1A通过类风湿关节炎患者通过TNFR2介导成纤维细胞样滑膜细胞迁移和印度刺猬信号通路。

类风湿关节炎(RA)是一种慢性自身免疫性疾病,其特征是关节发炎。RA成纤维样滑膜细胞(FLS)的侵略性特征之一是在局部环境中迁移的趋势,这在RA发病机理中起着核心作用。肿瘤坏死因子(TNF)样细胞因子1A(TL1A)是TNF超家族成员,在自身免疫中起作用,并通过TNF受体2(TNFR2)影响RA-FLS行为。我们研究了TNF样细胞因子的作用。 1A(TL1A)关于使用患者样本进行的RA-FLS迁移。具体来说,我们检查了刺猬信号通路,它是软骨细胞生长和分化的关键调节因子。我们发现TL1A显着增加了RA-FLS中的刺猬同源印第安刺猬(IHH)及其受体Patch 1,2,(PTCH 1,2)。此外,TL1A刺激的RA-FLS显着促进IHH蛋白表达。但是,用TNFR2拮抗剂阻断TL1A后,mRNA和蛋白质水平均大幅下降。TL1A刺激RA-FLS后,RA-FLS的迁移特性增强,但TL1A阻断后,RA-FLS的迁移特性受到损害。总之,我们的研究揭示了TL1A使用TNFR2调节RA-FLS迁移和印度刺猬信号通路。
更新日期:2018-05-18
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