Trabandt A, Aicher W K, Gay R E, Sukhatme V P, Fassbender H G, Gay S
Department of Medicine, University of Alabama, Birmingham 35294.
Rheumatol Int. 1992;12(2):53-9. doi: 10.1007/BF00300977.
In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could be detected in cytoplasmic extracts of collagenase-expressing synovial fibroblast-like cells when compared to equivalent RNA amounts isolated from control fibroblasts. Utilizing immunocytochemistry, immunoreactivity for c-fos oncoprotein was found in 13 of 19 joint specimens obtained from patients with active RA. These oncoprotein data were positively correlated to the collagenase expression in the same specimens. Moreover, immunohistochemical analysis confirmed the localization of both oncoprotein c-fos and fibroblast-type collagenase within synovial fibroblast-like cells attached to bone erosions.
鉴于间质胶原酶在类风湿关节炎（RA）发病机制中的重要作用，我们研究了类风湿滑膜中成纤维细胞型胶原酶的表达，并寻找其潜在的转录因子，即癌蛋白c-fos和早期生长反应基因-1（egr-1），一个可诱导的锌指编码基因。与从对照成纤维细胞分离的等量RNA相比，在表达胶原酶的滑膜成纤维样细胞的细胞质提取物中可检测到与c-fos和egr-1 cDNA探针互补的RNA序列水平升高。利用免疫细胞化学方法，在19例活动性RA患者的关节标本中，有13例检测到c-fos癌蛋白的免疫反应性。这些癌蛋白数据与同一样本中的胶原酶表达呈正相关。此外，免疫组织化学分析证实了癌蛋白c-fos和成纤维细胞型胶原酶在附着于骨侵蚀的滑膜成纤维样细胞内的定位。
