Department of Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Ir J Med Sci. 2019 Nov;188(4):1443-1449. doi: 10.1007/s11845-019-01978-w. Epub 2019 Feb 13.
BACKGROUND/OBJECTIVES: Recent studies suggest that, in addition to activation and hypersecretion of matrix components, fibroblasts from patients with systemic sclerosis (SSc) are resistant to apoptosis. Previous studies have shown that survivin, a member of inhibition of apoptosis (IAP) family, plays an important role in apoptosis resistance. Accordingly, we decided to study the expression of the most important members of IAP family in SSc fibroblasts, which can block apoptosis either by binding and inhibiting caspases or through caspase-independent mechanisms.
Skin biopsy samples were obtained from 19 patients with diffuse cutaneous SSc (DcSSc) and 16 healthy controls. Dermal fibroblasts were cultured and the total RNA was isolated from cells followed by cDNA synthesis. Real-time PCR was performed using SYBR Green PCR master mix and specific primers for cIAP1, cIAP2, XIAP, and Survivin mRNA quantification.
A significantly increased expression level of Survivin was observed in fibroblasts from SSc patients compared to controls (2.26-fold, P = 0.04). However, mRNA expression of cIAP1, cIAP2, and XIAP did not change significantly between cases and controls.
Our results showed that survivin is upregulated in SSc skin fibroblast which may lead to resistance to apoptosis. Further studies should be performed to reveal the role of survivin in apoptosis pathway of SSc fibroblasts.
背景/目的：最近的研究表明，除了基质成分的激活和过度分泌外，系统性硬皮病（SSc）患者的成纤维细胞还具有抗凋亡作用。先前的研究表明，凋亡抑制蛋白（IAP）家族的成员 survivin 在抗凋亡中发挥重要作用。因此，我们决定研究 IAP 家族中最重要的成员在 SSc 成纤维细胞中的表达情况，这些成员可以通过与半胱天冬酶结合并抑制其活性或通过半胱天冬酶非依赖性机制来阻断细胞凋亡。
从 19 例弥漫性皮肤硬皮病（DcSSc）患者和 16 例健康对照者的皮肤活检样本中获取皮肤组织，培养真皮成纤维细胞并提取细胞总 RNA，逆转录合成 cDNA。采用 SYBR Green PCR 试剂盒和特异性引物进行实时 PCR，定量检测 cIAP1、cIAP2、XIAP 和 Survivin mRNA 的表达。
与对照组相比，SSc 患者的成纤维细胞中 Survivin 的表达水平显著升高（2.26 倍，P = 0.04）。然而，cIAP1、cIAP2 和 XIAP 的 mRNA 表达在病例组和对照组之间没有明显变化。
我们的研究结果表明，SSc 皮肤成纤维细胞中 survivin 表达上调，可能导致其对凋亡的抵抗。需要进一步研究以揭示 survivin 在 SSc 成纤维细胞凋亡途径中的作用。
