Aicher W K, Heer A H, Trabandt A, Bridges S L, Schroeder H W, Stransky G, Gay R E, Eibel H, Peter H H, Siebenlist U
Clinical Research Group for Rheumatology (KFR), University of Freiburg Medical School, Germany.
J Immunol. 1994 Jun 15;152(12):5940-8.
In rheumatoid arthritis (RA) the proliferation of synovial lining cells appears to be one of the initial pathologic changes that contributes to the destruction of articular joints. To understand the pathomechanisms involved in these functional changes, we analyzed the transcriptional regulation of the zinc-finger gene 225 (Z-225/Egr-1), a transcription factor expressed in the immediate early events of cellular activation. We found that Z-225 transcripts were significantly up-regulated in RA synoviocytes. In primary and long term culture Z-225 was spontaneously transcribed at elevated levels. In situ hybridization of zinc-finger probe showed characteristic Z-225 transcripts in RA synovial tissues. Identity of these signals to the Z-225 gene product were confirmed in freshly isolated synovial tissue by enzymatic amplification of cDNA by the PCR technique. Z-225 transcripts were also detected and characterized in a cDNA library established from a RA synovial explant. We therefore conclude that RA synoviocytes spontaneously produce Z-225 gene products at elevated levels. Because early growth response gene Z-225 is involved in the regulation of expression of other genes such as proto-oncogenes c-ras and c-sis, which are also up-regulated in the RA synovium, activation of Z-225 transcription in RA may represent a key event in articular joint destruction.
在类风湿性关节炎（RA）中，滑膜衬里细胞的增殖似乎是导致关节破坏的初始病理变化之一。为了了解这些功能变化所涉及的病理机制，我们分析了锌指基因225（Z - 225/Egr - 1）的转录调控，该基因是一种在细胞激活的即刻早期事件中表达的转录因子。我们发现Z - 225转录本在RA滑膜细胞中显著上调。在原代和长期培养中，Z - 225以升高的水平自发转录。锌指探针的原位杂交显示RA滑膜组织中有特征性的Z - 225转录本。通过PCR技术对cDNA进行酶促扩增，在新鲜分离的滑膜组织中证实了这些信号与Z - 225基因产物的一致性。在从RA滑膜外植体建立的cDNA文库中也检测并鉴定了Z - 225转录本。因此，我们得出结论，RA滑膜细胞自发地以升高的水平产生Z - 225基因产物。由于早期生长反应基因Z - 225参与调控其他基因如原癌基因c - ras和c - sis的表达，而这些基因在RA滑膜中也上调，RA中Z - 225转录的激活可能代表关节破坏中的一个关键事件。
