Immunohistological localization of Notch receptors and their ligands Delta and Jagged in synovial tissues of rheumatoid arthritis
Immunohistological localization of Notch receptors and their ligands Delta and Jagged in synovial tissues of rheumatoid arthritis
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DOI：
10.1007/s00776-005-0943-3
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发表时间：
2005-11-01
影响因子：
1.7
通讯作者：
Shindo, H
中科院分区：
文献类型：
--
作者：
Yabe, Y;Matsumoto, T;Shindo, H
背景。Notch受体与其跨膜配体Delta和Jagged的相互作用不仅在多种组织的组织中起着重要作用，而且在多种遗传疾病和癌症的发展中也起着重要作用。Notch信号在类风湿关节炎（RA）中的功能参与已有报道，但Notch相关分子的表达谱及其与临床病理参数的关系尚不清楚。本研究分析了14例RA患者滑膜组织中4种Notch受体（Notch1-4）及其配体（Delta1和Jagged1）的免疫组化染色模式。Notch2和Notch4分别在少量样品和小血管的有限区域表达。Notch1、Notch3、Delta1和Jagged1在所有滑膜增生性病变的滑膜衬里和亚衬里细胞中均过表达。在淋巴滤泡T淋巴细胞和B淋巴细胞中也分别观察到Notch1的表达。通过共聚焦显微镜检测，Notch1和Notch3的表达与Jagged1重叠。利用Notch1裂解形式的特异性抗体鉴定了RA滑膜中Notch1信号的激活。这些分子的表达与临床病理参数无相关性。我们的研究结果表明，Notch信号在RA滑膜中被激活，但并不一定反映RA的病理状况。
Background. The interaction of Notch receptors with their transmembrane ligands Delta and Jagged plays an important role not only in the organization of a variety of tissues but also in several genetic disorders and cancer development. The functional involvement of the Notch signaling in rheumatoid arthritis (RA) has been reported previously, but the expression profile of Notch-related molecules, as well as their relation with clinicopathological parameters, remains unclear.Methods. In this study, we analyzed the immunohistochemical staining pattern of four Notch receptors (Notch1-4) and their ligands (Delta1 and Jagged1) in 14 synovial tissues obtained from 14 RA patients.Results. Notch2 and Notch4 were expressed in limited areas in a few samples or in small blood vessels, respectively. Notch1, Notch3, Delta1, and Jagged1 were overexpressed in the synovial lining and sublining cells on synovial hyperplastic lesions in all samples. Notch1 expression was also observed in T and B lymphocytes of lymphoid follicles independently. Notch1 and Notch3 expression overlapped with that of Jagged1, as determined by confocal microscopy. Activation of Notch1 signaling in the RA synovium was identified using a specific antibody to the cleaved form of Notch1. The expression of these molecules did not show any correlation with clinicopathological parameters.Conclusions. Our results suggest that Notch signaling is activated in RA synovium but does not necessarily reflect the pathological condition of RA.