Ebrahimiyan Hamidreza, Gharibdoost Farhad, Aslani Saeed, Kavosi Hoda, Farsad Faraneh, Jamshidi Ahmadreza, Mahmoudi Mahdi
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mod Rheumatol. 2020 Sep;30(5):862-869. doi: 10.1080/14397595.2019.1659545. Epub 2019 Sep 17.
Survivin is an important anti-apoptotic protein and is involved in increasing auto-reactivity during the autoimmune diseases like systemic sclerosis (SSc). In the current study, we investigate the expression level of total survivin (survivin-TS) and its three important variants alongside with evaluation of the expression level of important microRNAs (miRNAs) that are involved in survivin expression regulation. Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls, 25 diffuse cutaneous SSc (DcSSc), and 25 limited cutaneous SSc (LcSSc) patients. RNA was extracted and single-strand cDNA was synthesized. Quantitative real-time PCR was used to evaluate the expression level of survivin-TS and its variants as well the miRNAs. Overexpression of survivin-2B and downregulation of survivin wild-type (survivin-WT) were found in total-SSc patients; however, expression level of survivin-TS had no significant difference. The expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, miR-218-5p and miR-708-5p were higher in total-SSc patients. Significantly negative correlations were found between transcript levels of miR-150-5p, miR-16-5p, and miR-485-5p with survivin-TS mRNA expression. Survivin variants had altered expression in total-SSc patients. In addition, miRNAs might potentially and negatively regulate the survivin-TS expression. Altered expression of survivin, regulated by miRNAs, may result in apoptosis resistance and auto-reactivity in lymphocytes from patients and have important roles in SSc pathogenicity.
生存素是一种重要的抗凋亡蛋白,在系统性硬化症(SSc)等自身免疫性疾病中参与增强自身反应性。在本研究中,我们调查了总生存素(survivin-TS)及其三个重要变体的表达水平,并评估了参与生存素表达调控的重要微小RNA(miRNA)的表达水平。从50名健康对照者、25名弥漫性皮肤型SSc(DcSSc)患者和25名局限性皮肤型SSc(LcSSc)患者中分离外周血单个核细胞(PBMC)。提取RNA并合成单链cDNA。采用定量实时PCR评估survivin-TS及其变体以及miRNA的表达水平。在总SSc患者中发现survivin-2B过表达和生存素野生型(survivin-WT)下调;然而,survivin-TS的表达水平无显著差异。总SSc患者中miR-335-5p、miR-485-5p、miR-16-5p、miR-150-5p、miR-34a-5p、miR-218-5p和miR-708-5p的表达水平较高。发现miR-150-5p、miR-16-5p和miR-485-5p的转录水平与survivin-TS mRNA表达之间存在显著负相关。生存素变体在总SSc患者中表达改变。此外,miRNA可能潜在地负调控survivin-TS的表达。由miRNA调控的生存素表达改变可能导致患者淋巴细胞的凋亡抵抗和自身反应性,并在SSc发病机制中起重要作用。