Objective: To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis.
Methods: Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes α-SMA, COL1A1, COL1A2, and COL3A1 were detected using RT-PCR; the proliferation of the cells was assessed using a real-time cell proliferation detection system.
Results: Compared with those in normal skin samples, the mRNA and protein expressions of PTTG1 increased significantly in the skin tissue of patients with SSc (P < 0.05). In cultured primary skin fibroblasts, the expression of PTTG1 mRNA was positively correlated with those of α-SMA (R2=0.8192, P < 0.05), COL1A1 (R2=0.6398, P < 0.05), COL1A2 (R2=0.316, P < 0.05) and COL3A1 mRNAs (R2=0.3727, P < 0.05). Interference of PTTG1 expression significantly inhibited the cell proliferation, obviously lowered the expressions of fibrosis-related genes, and down-regulated the expression of collagen in the fibroblasts.
Conclusions: PTTG1 is highly expressed in skin tissues of patients with SSc, and PTTG1 knockdown can reduce the activity of the dermal fibroblasts, suggesting a close correlation of PTTG1 with fibrosis in SSc.
目的: 研究垂体肿瘤转化基因（PTTG1）在系统性硬化症（SSc）中的表达及其对成纤维细胞的作用。
方法: 收集皮肤活检组织，其中SSc患者组21例，正常组22例。分别应用实时荧光定量聚合酶链式反应法（Real-time PCR）检测皮肤组织中PTTG1基因表达水平；应用免疫组化方法检测皮肤组织中PTTG1蛋白表达水平；应用小干扰RNA（siRNA）降低成纤维细胞中PTTG1基因表达，通过Real-time PCR方法检测细胞中PTTG1及与细胞纤维化密切相关的几个基因α-SMA、COL1A1、COL1A2、COL3A1的表达变化；通过细胞实时增殖检测系统检测细胞增殖。
结果: 与正常对照相比，SSc患者皮肤组织中PTTG1的表达水平明显升高，差异具有统计学意义（P < 0.05）；与正常对照相比，SSc患者皮肤组织中阳性细胞增多，PTTG1蛋白表达明显升高；原代皮肤成纤维细胞中PTTG1表达水平和α-SMA、COL1A1、COL1A2、COL3A1均存在正相关，差异具有统计学意义（R2= 0.8192，P < 0.05；R2=0.6398，P < 0.05；R2=0.316，P < 0.05；R2=0.3723，P < 0.05）；同时，原代皮肤成纤维细胞中PTTG1干扰后，细胞增殖被显著抑制，纤维化相关基因（COL1A1、COL1A2、PAI-1）表达下降，胶原蛋白的基因表达降低。
结论: SSc患者中存在PTTG1过度表达，干扰PTTG1可降低成纤维细胞活性，提示PTTG1与SSc纤维化程度密切相关。
Keywords: cell proliferation; fibroblasts; fibrosis; systemic sclerosis; tumor-transforming gene-1.