MiR-155-5p modulates inflammatory phenotype of activated oral lichen-planus-associated-fibroblasts by targeting SOCS1
MiR-155-5p modulates inflammatory phenotype of activated oral lichen-planus-associated-fibroblasts by targeting SOCS1
复制标题
DOI：
10.1007/s11033-022-07603-x
复制
发表时间：
2022-06-22
影响因子：
2.8
通讯作者：
Fan, Yuan
中科院分区：
文献类型：
--
作者：
Cheng, Juehua;Zhang, Yuyao;Fan, Yuan
研究背景口腔扁平苔藓（Oral lichen planus，OLP）是一种慢性炎症性口腔粘膜疾病。细胞因子与OLP的发生密切相关。除免疫细胞外，据报道成纤维细胞也可诱导局部炎症。据报道，MicroRNA（miR）-155-5p在OLP中显著增加，并且已知其调节炎症。本研究旨在探讨miR-155- 5 p在OLP病变成纤维细胞中的作用。方法和结果从15例健康对照和30例OLP患者的口腔粘膜中分离正常粘膜成纤维细胞（NF）和OLP相关成纤维细胞（OLP AFs）。采用定量RT-PCR检测miR-155- 5 p和成纤维细胞活化蛋白α（FAP-α）的表达，并分析其相关性。使用ELISA测定白细胞介素（IL）-6和IL-8水平。免疫印迹法检测细胞因子信号抑制因子（SOCS）1的表达。进行双荧光素酶报告基因测定以研究miR-155- 5 p和SOCS 1之间的相互作用。miR-155- 5 p和FAP-α在OLP AF中显著增加并且正相关。miR-155- 5 p在OLP AFs中的过表达增加了IL-6和IL-8的释放并降低了SOCS 1的表达，而miR-155- 5 p在OLP AFs中的敲低降低了IL-6和IL-8的释放。SOCS 1在OLP AFs中表达下调，SOCS 1沉默增加OLP AFs中IL-6和IL-8的产生。此外，miR-155- 5 p通过直接靶向OLP AF中SOCS 1的3 '-UTR来抑制SOCS 1的表达。结论miR-155- 5 p通过下调SOCS 1的表达，调节OLP AFs分泌IL-6和IL-8。我们的研究结果为OLP的发病机制提供了新的见解，并确定了OLP治疗的潜在新靶点。
Background Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines are closely associated with OLP development. In addition to immune cells, fibroblasts have been reported to induce regional inflammation. MicroRNA(miR)-155-5p is reportedly increased significantly in OLP and is known to regulate inflammation. This study aimed to investigate the role of miR-155-5p in fibroblasts of OLP lesions. Methods and results Normal mucosal fibroblasts (NFs) and OLP associated-fibroblasts (OLP AFs) were isolated from the oral mucosa of 15 healthy controls and 30 OLP patients. We detected the expression of miR-155-5p and fibroblast activation protein alpha (FAP-alpha) using quantitative RT-PCR and analyzed their correlation. Interleukin (IL)-6 and IL-8 levels were determined using ELISA. Expression of suppressor of cytokine signaling (SOCS) 1 was analyzed by western blotting. A dual-luciferase reporter assay was performed to investigate the interaction between miR-155-5p and SOCS1. MiR-155-5p and FAP-alpha were significantly increased and positively correlated in OLP AFs. Overexpression of miR-155-5p in OLP AFs augmented IL-6 and IL-8 release and decreased SOCS1 expression, whereas knockdown of miR-155-5p in OLP AFs decreased IL-6 and IL-8 release. The expression of SOCS1 was downregulated in OLP AFs, and SOCS1 silencing augmented IL-6 and IL-8 production in OLP AFs. Furthermore, miR-155-5p inhibited SOCS1 expression by directly targeting its 3 '-UTR in OLP AFs. Conclusions MiR-155-5p regulates the secretion of IL-6 and IL-8 by downregulating the expression of SOCS1 in activated OLP AFs. Our results provide novel insights into the pathogenesis of OLP and identify a potential new target for OLP therapy.