靶向 microRNA-190a 可通过上调 Krüppel 样因子 15 阻止口腔黏膜下纤维化中持续存在的肌成纤维细胞活化和氧化应激积累

IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
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引用次数: 0

摘要

背景/目的口腔黏膜下纤维化(OSF)是一种以炎症和胶原过度沉积为特征的疾病,已被确定为一种潜在的恶性疾病。最近,一些微RNA(miRNA)被证明与纤维化相关的各种疾病有牵连。然而,人们对这些 miRNA 如何调节 OSF 的发展还知之甚少。材料与方法通过RNA测序和qRT-PCR证实了潜在的促纤维化miRNA在OSF队列和原发性颊粘膜成纤维细胞中的表达和临床意义。利用荧光素酶报告活性测定、miRNA模拟物或抑制剂以及短发夹RNA沉默来阐明miRNA的分子机制。结果这项研究表明,miR-190a在纤维化的口腔粘膜成纤维细胞(fBMFs)中过度表达。用 miR-190a 抑制剂转染 fBMFs 可减少细胞迁移、胶原凝胶收缩、ROS 生成和纤维化标记物的表达。此外,miR-190a 是通过与其靶标 Krüppel-like factor 15(KLF15)直接结合而发挥这种促纤维化特性的。结论我们的研究结果表明,miR-190a 参与了肌成纤维细胞的活化,这表明以 miR-190a/KLF15 轴为靶点可能是治疗 OSF 的一种可行方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting microRNA-190a halts the persistent myofibroblast activation and oxidative stress accumulation through upregulation of Krüppel-like factor 15 in oral submucous fibrosis

Background/purpose

Oral submucous fibrosis (OSF) is a condition characterized by inflammation and excessive collagen deposition, which has been identified as a potentially malignant disorder. Recently, several microRNAs (miRNAs) have been shown to be implicated in various disorders associated with fibrosis. However, how these miRNAs modulate OSF development is poorly understood. Therefore, the study aimed to identify the specific miRNAs that contribute to the progression of OSF and to investigate their molecular mechanisms in promoting fibrosis.

Materials and methods

The expression and clinical significance of potential pro-fibrosis miRNA in the OSF cohort and primary buccal mucosal fibroblasts were confirmed through RNA sequencing and qRT–PCR. Luciferase reporter activity assay, miRNA mimic or inhibitor, and short-hairpin RNA silencing were used to elucidate the molecular mechanism of miRNA. Transwell migration, collagen contraction, and reactive oxygen species (ROS) generation detection were used to investigate the effects of this mechanism on the myofibroblast phenotype and cellular pro-fibrosis capacity.

Results

This study demonstrated that miR-190a was overexpressed in fibrotic buccal mucosal fibroblasts (fBMFs). Transfecting fBMFs with miR-190a inhibitor resulted in reduced cell migration, collagen gel contraction, ROS generation, and expression of fibrotic markers. Furthermore, miR-190a exerted this pro-fibrosis property by direct binding to its target, Krüppel-like factor 15 (KLF15). The results also indicated that the aberrant upregulation of miR-190a, in turn, downregulated the expression of KLF15, which resulted in the activation of myofibroblast.

Conclusion

Our findings demonstrated that miR-190a was involved in myofibroblast activation, suggesting that targeting the miR-190a/KLF15 axis may be a feasible approach in the therapy of OSF.

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来源期刊
Journal of Dental Sciences
Journal of Dental Sciences 医学-牙科与口腔外科
CiteScore
5.10
自引率
14.30%
发文量
348
审稿时长
6 days
期刊介绍: he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.
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