Ming-Yung Chou , Chia-Hsuan Lee , Pei-Ling Hsieh , Shih-Chi Chao , Chuan-Hang Yu , Yi-Wen Liao , Shiao-Pieng Lee , Cheng-Chia Yu , Jun-Yang Fan
{"title":"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","authors":"Ming-Yung Chou , Chia-Hsuan Lee , Pei-Ling Hsieh , Shih-Chi Chao , Chuan-Hang Yu , Yi-Wen Liao , Shiao-Pieng Lee , Cheng-Chia Yu , Jun-Yang Fan","doi":"10.1016/j.jds.2024.07.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background/purpose</h3><p>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.</p></div><div><h3>Materials and methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":15583,"journal":{"name":"Journal of Dental Sciences","volume":"19 4","pages":"Pages 1999-2006"},"PeriodicalIF":3.4000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1991790224002228/pdfft?md5=1506873d19b98b6eaa0667d1d14d1157&pid=1-s2.0-S1991790224002228-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Targeting microRNA-190a halts the persistent myofibroblast activation and oxidative stress accumulation through upregulation of Krüppel-like factor 15 in oral submucous fibrosis\",\"authors\":\"Ming-Yung Chou , Chia-Hsuan Lee , Pei-Ling Hsieh , Shih-Chi Chao , Chuan-Hang Yu , Yi-Wen Liao , Shiao-Pieng Lee , Cheng-Chia Yu , Jun-Yang Fan\",\"doi\":\"10.1016/j.jds.2024.07.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background/purpose</h3><p>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.</p></div><div><h3>Materials and methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":15583,\"journal\":{\"name\":\"Journal of Dental Sciences\",\"volume\":\"19 4\",\"pages\":\"Pages 1999-2006\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1991790224002228/pdfft?md5=1506873d19b98b6eaa0667d1d14d1157&pid=1-s2.0-S1991790224002228-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Dental Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1991790224002228\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Dental Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1991790224002228","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
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.
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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