Giovannetti Francesca, Pontecorvi Paola, Megiorni Francesca, Armentano Marta, Alisi Ludovico, Romano Enrico, Marchese Cinzia, Lambiase Alessandro, Bruscolini Alice
Department of Sense Organs, Sapienza University of Rome, Rome, Italy.
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):80. doi: 10.1167/iovs.66.4.80.
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by inflammation and tissue destruction of the salivary and lacrimal glands, leading to sicca symptoms. Dysregulation of microRNAs (miRNAs), key post-transcriptional regulators, has been implicated in pSS, but their role in conjunctival epithelial cells (CECs) remains unclear. This study aimed to identify altered miRNA expression patterns in CEC from patients with pSS and their potential involvement in pSS pathogenesis.
CEC samples were collected from six patients with pSS and six healthy controls (HCs) using nylon-tipped swabs. The miRNA expression was profiled using the NanoString nCounter system with minimal RNA input. Differentially expressed (DE) miRNAs were identified via ROSALIND software, and bioinformatics tools (miRNet and miRTargetLink) were applied to construct miRNA-centric networks, predict target genes, and perform pathway enrichment analysis.
We identified 11 DE miRNAs in patients with pSS compared with the HCs. Key miRNAs, including hsa-miR-548j-3p and hsa-miR-219b-3p, are central to immune and inflammatory regulation pathways. Pathway enrichment analysis highlighted their involvement in processes such as immune cell regulation, inflammatory signaling, and glandular damage. Dysregulated miRNAs modulate key targets, like TNFAIP3, IL6R, IFNAR1, IL7, and ICOSLG, suggesting their potential role in pSS pathogenesis.
This study underscores the potential of miRNAs as biomarkers and therapeutic targets in pSS-associated dry eye disease. Despite limitations like small sample size and reliance on in silico predictions, our findings provide valuable insights into miRNA-mediated regulation of immune responses and inflammation, paving the way for future diagnostic and therapeutic advancements.
原发性干燥综合征（pSS）是一种慢性自身免疫性疾病，其特征是唾液腺和泪腺发生炎症和组织破坏，导致口干和眼干症状。微小RNA（miRNA）作为关键的转录后调节因子，其失调与pSS有关，但其在结膜上皮细胞（CEC）中的作用仍不清楚。本研究旨在确定pSS患者CEC中miRNA表达模式的改变及其在pSS发病机制中的潜在作用。
使用尼龙头拭子从6例pSS患者和6例健康对照（HC）中收集CEC样本。使用NanoString nCounter系统以最少的RNA输入量对miRNA表达进行分析。通过ROSALIND软件鉴定差异表达（DE）的miRNA，并应用生物信息学工具（miRNet和miRTargetLink）构建以miRNA为中心的网络、预测靶基因并进行通路富集分析。
与HC相比，我们在pSS患者中鉴定出11种DE miRNA。关键的miRNA，包括hsa-miR-548j-3p和hsa-miR-219b-3p，在免疫和炎症调节途径中起核心作用。通路富集分析突出了它们参与免疫细胞调节、炎症信号传导和腺体损伤等过程。失调的miRNA调节关键靶标，如TNFAIP3、IL6R、IFNAR1、IL7和ICOSLG，表明它们在pSS发病机制中的潜在作用。
本研究强调了miRNA作为pSS相关干眼症生物标志物和治疗靶点的潜力。尽管存在样本量小和依赖计算机预测等局限性，但我们的研究结果为miRNA介导的免疫反应和炎症调节提供了有价值的见解，为未来的诊断和治疗进展铺平了道路。
