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在活动期类风湿关节炎患者的滑膜组织中自噬水平升高,且与疾病严重程度相关。

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

作者信息

Zhu Li, Wang Huaizhou, Wu Yu, He Zhengwen, Qin Yanghua, Shen Qian

机构信息

Department of Laboratory Medicine, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China; Department of Laboratory Diagnosis, Changhai Hospital of the Second Military Medical University, Shanghai 200433, China.

Department of Laboratory Diagnosis, Changhai Hospital of the Second Military Medical University, Shanghai 200433, China.

出版信息

Mediators Inflamm. 2017;2017:7623145. doi: 10.1155/2017/7623145. Epub 2017 Feb 1.

Abstract

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 ( = 20) were significantly higher than those in OA patients ( = 16). We further showed that the LC3-II/-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.

摘要

类风湿关节炎(RA)是一种复杂且尚未完全了解的自身免疫性疾病,与多关节损伤相关。主要效应细胞滑膜成纤维细胞具有抗凋亡和增生特性,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了类风湿关节炎患者和骨关节炎(OA)患者在关节置换手术时获取的滑膜组织的自噬状态。我们还使用SPSS进一步评估了自噬水平与RA活动相关血清标志物之间的相关性。结果显示,活动期类风湿关节炎患者(n = 20)滑膜组织中自噬相关蛋白(贝林1、自噬相关蛋白5和微管相关蛋白1轻链3)的表达水平(mRNA和蛋白质水平)显著高于OA患者(n = 16)。我们进一步表明,微管相关蛋白1轻链3-II/肌动蛋白相对灰度值与几种RA活动相关标志物的血清水平密切相关:C反应蛋白(CRP)、红细胞沉降率(ESR)、环瓜氨酸肽(CCP)和类风湿因子(RF)。我们的结果表明,评估滑膜活检的自噬水平可能是诊断RA和评估疾病活动的一种有用方法。降低自噬相关基因的表达水平可能成为活动期类风湿关节炎的一个新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bf9/5309404/f4ef3132210e/MI2017-7623145.001.jpg

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