The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity.

The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity.
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活动性类风湿关节炎患者滑膜组织中的自噬水平升高,且与疾病严重程度相关

DOI:
10.1155/2017/7623145
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发表时间:
2017
影响因子:
4.6
通讯作者:
Shen Q
Shen Q
中科院分区:
医学3区
文献类型:
--
作者:
Zhu L;Wang H;Wu Y;He Z;Qin Y;Shen Q

文献摘要

被引文献

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类风湿性关节炎(RA)是一种复杂的自身免疫性疾病,其与多关节损伤有关,尚未完全了解。滑膜成纤维细胞是主要的效应细胞,具有抗凋亡性和增生性,这表明滑膜组织中的自噬水平较高。本文采用实时荧光定量PCR、免疫细胞化学和蛋白质印迹法研究RA和OA患者关节置换术时滑膜组织的自噬状态。我们进一步评估自噬水平与RA活动相关血清标志物之间的相关性。结果显示,活动性类风湿关节炎患者(n = 20)滑液组织中自噬相关蛋白(belcin 1、Atg 5和LC 3)的表达水平(mRNA和蛋白质水平)明显高于OA患者(n = 16)。我们进一步发现,LC 3-II/β-actin的相对灰度值与几种RA活动相关标志物的血清水平密切相关:CRP、ESR、CCP和RF。我们的研究结果表明,评估滑膜活检的自噬水平可能是一个有用的方法来诊断类风湿关节炎和估计疾病的活动。降低自噬相关基因的表达水平可能成为治疗活动期类风湿关节炎的新靶点。
Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n = 20) were significantly higher than those in OA patients (n = 16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.