Department of Oral Mucosal Diseases, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Mol Biol Rep. 2022 Aug;49(8):7783-7792. doi: 10.1007/s11033-022-07603-x. Epub 2022 Jun 22.
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.
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-α) 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-α 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.
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.
口腔扁平苔藓（OLP）是一种慢性炎症性口腔黏膜疾病。细胞因子与 OLP 的发展密切相关。除免疫细胞外，已有报道称成纤维细胞可诱导局部炎症。据报道，miR-155-5p 在 OLP 中显著增加，并且已知可调节炎症。本研究旨在探讨 miR-155-5p 在 OLP 病变成纤维细胞中的作用。
从 15 名健康对照者和 30 名 OLP 患者的口腔黏膜中分离出正常黏膜成纤维细胞（NFs）和 OLP 相关成纤维细胞（OLP AFs）。我们使用定量 RT-PCR 检测 miR-155-5p 和成纤维细胞激活蛋白α（FAP-α）的表达，并分析它们之间的相关性。使用 ELISA 测定白细胞介素（IL）-6 和 IL-8 的水平。通过 Western blot 分析抑制细胞因子信号（SOCS）1 的表达。进行双荧光素酶报告基因检测以研究 miR-155-5p 与 SOCS1 之间的相互作用。在 OLP AFs 中，miR-155-5p 和 FAP-α 的表达显著增加且呈正相关。在 OLP AFs 中转染 miR-155-5p 可增加 IL-6 和 IL-8 的释放并降低 SOCS1 的表达，而在 OLP AFs 中转染 miR-155-5p 可减少 IL-6 和 IL-8 的释放。在 OLP AFs 中 SOCS1 的表达下调，并且 SOCS1 沉默可增加 OLP AFs 中 IL-6 和 IL-8 的产生。此外，miR-155-5p 通过直接靶向 OLP AFs 中的 3'-UTR 来抑制 SOCS1 的表达。
miR-155-5p 通过下调激活的 OLP AFs 中 SOCS1 的表达来调节 IL-6 和 IL-8 的分泌。我们的结果为 OLP 的发病机制提供了新的见解，并确定了 OLP 治疗的新潜在靶点。
