Decreased semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis.
Decreased semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis.
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DOI：
10.1186/1471-2474-14-40
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发表时间：
2013-01-23
影响因子：
2.3
通讯作者：
Saito T
中科院分区：
文献类型：
--
作者：
Takagawa S;Nakamura F;Kumagai K;Nagashima Y;Goshima Y;Saito T
类风湿性关节炎（RA）是一种自身免疫性疾病，其发病机制尚不完全清楚。信号蛋白3a （Sema3A）具有免疫调节作用。Neuropilin1 （NRP1）是Sema3A的主要受体，也是血管内皮生长因子165 （VEGF165）的受体。研究表明，Sema3A可竞争性地拮抗VEGF165信号。本研究探讨Sema3A是否在RA患者滑膜组织中表达，并与疾病活动性和滑膜组织组织学特征相关。从类风湿性关节炎（RA）和骨关节炎（OA）患者中获得人类滑膜组织样本。使用基于c反应蛋白（DAS28-CRP）的28关节疾病活动评分来计算RA患者的疾病活动性。采用鲁尼炎症评分系统评价RA滑膜组织的组织学特征。免疫组织化学方法测定滑膜组织中Sema3A、VEGF165和NRP1阳性细胞的定位。采用实时定量聚合酶链反应（qPCR）检测Sema3A、VEGF-A和NRP1 mRNA的表达水平。在OA标本中，Sema3A、VEGF165和NRP1蛋白在滑膜内层和内层下的炎症细胞中表达。免疫组化显示，与OA相比，RA组织滑膜衬里细胞中Sema3A蛋白表达降低。qPCR分析显示，RA滑膜组织样品中的Sema3A mRNA水平明显低于OA， Sema3A/VEGF-A mRNA表达水平与DAS28-CRP的比值显著相关（R = - 0.449, p = 0.013）。Sema3A mRNA水平也与鲁尼炎症评分相关，尤其是在淋巴细胞血管周围浸润（R = - 0.506, p = 0.004）、淋巴细胞局灶性聚集（R = - 0.501, p = 0.005）和淋巴细胞弥漫性浸润（R = - 0.536, p = 0.002）。RA滑膜组织中Sema3A表达的减少可能与RA的发病有关。
Rheumatoid arthritis (RA) is an autoimmune disease of which the pathogenetic mechanisms are not fully understood. Semaphorin3A (Sema3A) has an immune regulatory role. Neuropilin1 (NRP1), the primary receptor for Sema3A, is also a receptor for vascular endothelial growth factor 165 (VEGF165). It has been shown that Sema3A competitively antagonizes VEGF165 signaling. This study investigated whether Sema3A is expressed in synovial tissues, and is associated with disease activity and the histological features of synovial tissues from RA patients. Human synovial tissues samples were obtained from RA and osteoarthritis (OA) patients. Disease activity of RA patients was calculated using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The histological features of RA synovial tissues were evaluated using Rooney’s inflammation scoring system. The localization of Sema3A, VEGF165 and NRP1 positive cells was immunohistochemically determined in synovial tissues. Expression levels of Sema3A, VEGF-A and NRP1 mRNA were determined using quantitative real-time polymerase chain reaction (qPCR). In OA specimens, Sema3A, VEGF165 and NRP1 proteins were expressed in the synovial lining and inflammatory cells beneath the lining. Immunohistochemistry revealed the protein expression of Sema3A in synovial lining cells was decreased in RA tissues compared with OA samples. qPCR analysis demonstrated a significant reduction of Sema3A mRNA levels in RA synovial tissue samples than in OA and a significant correlation of the ratio of Sema3A/VEGF-A mRNA expression levels with DAS28-CRP (R = −0.449, p = 0.013). Sema3A mRNA levels also correlated with Rooney’s inflammation score, especially in perivascular infiltrates of lymphocytes (R = −0.506, p = 0.004), focal aggregates of lymphocytes (R = −0.501, p = 0.005) and diffuse infiltrates of lymphocytes (R = −0.536, p = 0.002). Reduction of Sema3A expression in RA synovial tissues may contribute to pathogenesis of RA.
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影响因子：
4.4
作者：
Kim, Wan-Uk;Kang, Soon Suk;Cho, Chul-Soo
通讯作者：
Cho, Chul-Soo
影响因子：
20.3
作者：
Acevedo, Lisette M.;Barillas, Samuel;Cheresh, David A.
通讯作者：
Cheresh, David A.
影响因子：
8.6
作者：
Clavel, Gaeelle;Bessis, Natacha;Boissier, Marie-Christophe
通讯作者：
Boissier, Marie-Christophe
影响因子：
4.4
作者：
Catalano, Alfonso
通讯作者：
Catalano, Alfonso
DOI：
10.2183/pjab.86.611
发表时间：
2010
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Kumanogoh A;Kikutani H
通讯作者：
Kikutani H