Liu Yixuan, Guo Liuxiong, Cao Jingjing, Ning Xiaoran, Zheng Xiao, Li Fang, Song Guangyao
Department of Rheumatology and Immunology, Hebei General Hospital, Shijiazhuang, Hebei, 050011, China; Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei, 050011, China.
Biochem Biophys Res Commun. 2025 Apr 12;758:151647. doi: 10.1016/j.bbrc.2025.151647. Epub 2025 Mar 17.
Sjögren's syndrome (SS) is a chronic systemic autoimmune It chiefly impacts the exocrine glands, specifically the salivary and lacrimal ones, causing manifestations such as dry mouth and eye. Sjögren's syndrome often coexists with other autoimmune diseases, making it difficult to study its pathogenesis. Mounting evidence suggests that microRNAs (miRNAs) play a pivotal role in the development of autoimmune diseases, yet the precise mechanisms underlying their involvement in SS remain to be fully elucidated.
A cohort dataset pertaining to Sjögren's syndrome was procured from the Gene Expression Omnibus (GEO) database and subsequently analyzed using bioinformatics tools. The association between Signal Transducer and Activator of Transcription 1 (STAT1) and Sjögren's syndrome is well-established. To predict miRNAs targeting STAT1, we utilized the TargetScan database, focusing on miR-216a-3p. Furthermore, to model primary Sjögren's syndrome (pSS) in vivo, we employed a rat model established through submandibular gland protein immunization. These pSS model rats were then subjected to injections of either miR-216a-3p mimics or inhibitors. Subsequently, histological analysis was conducted to assess the resulting tissue morphology. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was employed to determine the expression levels of both STAT1 and miR-216a-3p. Cytokine levels were quantified using enzyme-linked immunosorbent assay (ELISA). To investigate the protein expression of key components of the STAT/JAK signaling pathway, Western blot analysis was performed, targeting Signal Transducer and Activator of Transcription 1 (STAT1), Janus kinase 1 (JAK1), and Janus kinase 2 (JAK2).
Our findings indicate that miR-216a-3p exerts regulatory control over the JAK/STAT signaling pathway by modulating the phosphorylation of STAT1, thereby attenuating the severity of primary Sjögren's syndrome in our model. Moreover, miR-216a-3p was observed to inhibit the secretion of pro-inflammatory cytokines and mitigate B cell hyperactivation. These results collectively suggest a potentially significant role for miR-216a-3p in the pathogenesis of autoimmune diseases, warranting further investigation.
干燥综合征（SS）是一种慢性全身性自身免疫性疾病。它主要影响外分泌腺，特别是唾液腺和泪腺，导致口干、眼干等症状。干燥综合征常与其他自身免疫性疾病共存，这使得研究其发病机制变得困难。越来越多的证据表明，微小RNA（miRNA）在自身免疫性疾病的发展中起关键作用，但其参与干燥综合征的确切机制仍有待充分阐明。
从基因表达综合数据库（GEO）中获取与干燥综合征相关的队列数据集，随后使用生物信息学工具进行分析。信号转导和转录激活因子1（STAT1）与干燥综合征之间的关联已得到充分证实。为了预测靶向STAT1的miRNA，我们利用TargetScan数据库，重点关注miR-216a-3p。此外，为了在体内建立原发性干燥综合征（pSS）模型，我们采用了通过下颌下腺蛋白免疫建立的大鼠模型。然后对这些pSS模型大鼠注射miR-216a-3p模拟物或抑制剂。随后，进行组织学分析以评估由此产生的组织形态。采用定量实时逆转录聚合酶链反应（qRT-PCR）来测定STAT1和miR-216a-3p的表达水平。使用酶联免疫吸附测定（ELISA）对细胞因子水平进行定量。为了研究STAT/JAK信号通路关键成分的蛋白表达，进行了蛋白质印迹分析，检测信号转导和转录激活因子1（STAT1）、Janus激酶1（JAK1）和Janus激酶2（JAK2）。
我们的研究结果表明，miR-216a-3p通过调节STAT1的磷酸化对JAK/STAT信号通路发挥调控作用，从而减轻我们模型中原发性干燥综合征的严重程度。此外，观察到miR-216a-3p抑制促炎细胞因子的分泌并减轻B细胞的过度活化。这些结果共同表明miR-216a-3p在自身免疫性疾病发病机制中可能具有重要作用，值得进一步研究。
