Szabo Iulia, Muntean Laura, Crisan Tania, Rednic Voicu, Sirbe Claudia, Rednic Simona
Department of Rheumatology, "Iuliu Hațieganu" University of Medicine and Pharmacy Cluj-Napoca, 400000 Cluj-Napoca, Romania.
Department of Rheumatology, County Emergency Hospital Cluj-Napoca, 400000 Cluj-Napoca, Romania.
Biomedicines. 2021 Oct 14;9(10):1471. doi: 10.3390/biomedicines9101471.
Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets.
系统性硬化症（SSc）是一种罕见的结缔组织疾病，具有异质性临床表型。它的特征在于致病三联征：微血管病变、免疫功能障碍和纤维化。表观遗传机制在不干扰DNA序列的情况下调节基因表达。表观遗传标记可能是可逆的，它们对外界刺激的不同反应可以解释SSc的多变临床表现，同时为靶向药物开发提供机会。小的非编码RNA序列（miRNA）已证明在脉管系统、免疫激活和细胞外基质之间存在复杂的相互作用。在SSc皮肤标本和含有多种失调miRNA的血液样本中鉴定出了不同的miRNA谱。它们的靶基因主要参与促纤维化途径，但新的证据也证实它们参与了血管生成受损和异常免疫反应。专注于疾病早期阶段以及各种组织中miRNA差异表达的研究方法可能会为SSc发病机制带来新的见解，并验证miRNA作为生物标志物和治疗靶点的临床效用。
