Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and osteoarthritis
Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and osteoarthritis
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DOI：
10.1007/s00296-003-0316-1
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Kosmehl, H
中科院分区：
文献类型：
--
作者：
Kriegsmann, J;Berndt, A;Kosmehl, H
目标。本研究的目的是明确和比较纤维连接蛋白(FN)亚型在类风湿关节炎(RA)和骨关节炎(OA)患者滑膜组织中的表达。方法：研究方法。用抗总FN、特异区(ED)-A FN、ED-B FN和肿瘤胎儿糖基化FN的单抗，研究FN亚型在滑膜中的表达。此外，应用原位杂交技术检测ED-B FN mRNA，包括检测细胞类型的双标记技术。结果。RA和OA滑膜衬里均可见总FN、ED-A FN、癌胎糖化FN和少量ED-B FN的强表达。类风湿关节炎组织中FN亚型在间质和血管中的表达更为显著。血管疙瘩组织与ED-B FN呈强阳性标记。结论。选择性剪接的FN亚型的表达与组织重塑有关，并且作为这种现象的部分过程，与新生血管有关，而不是与潜在的疾病、X射线状态或急性炎症参数有关。在衬里层，FN的表达与细胞募集相关的增生有关，但与增殖状态无关。最值得注意的是，ED-B FN在血管疙瘩组织中的表达似乎与RA组织中描述的侵袭性表型有关。
Objective. The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied. Results. Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression of Fn isoforms was more prominent in RA tissue. Pannus tissue showed strong labeling with ED-B Fn. Conclusion. The expression of alternatively spliced isoforms of Fn is associated with tissue remodeling and, as a partial process of this phenomenon, with neovascularization rather than underlying disease, X-ray status, or parameters of acute inflammation. In the lining layer, Fn expression correlates with hyperplasia associated with cell recruitment but not with proliferative status. Most remarkably, the expression of ED-B Fn in pannus tissue seems to be associated with the invasive phenotype described in RA tissue.