源自上皮细胞的外泌体 miR-17-5p 参与了上皮细胞与成纤维细胞的异常串扰,并诱发了口腔黏膜下纤维化的发展。

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2024-06-20 DOI:10.1038/s41368-024-00302-2
Changqing Xie, Liang Zhong, Hui Feng, Rifu Wang, Yuxin Shi, Yonglin Lv, Yanjia Hu, Jing Li, Desheng Xiao, Shuang Liu, Qianming Chen, Yongguang Tao
{"title":"源自上皮细胞的外泌体 miR-17-5p 参与了上皮细胞与成纤维细胞的异常串扰,并诱发了口腔黏膜下纤维化的发展。","authors":"Changqing Xie, Liang Zhong, Hui Feng, Rifu Wang, Yuxin Shi, Yonglin Lv, Yanjia Hu, Jing Li, Desheng Xiao, Shuang Liu, Qianming Chen, Yongguang Tao","doi":"10.1038/s41368-024-00302-2","DOIUrl":null,"url":null,"abstract":"<p><p>Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"48"},"PeriodicalIF":10.8000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187069/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis.\",\"authors\":\"Changqing Xie, Liang Zhong, Hui Feng, Rifu Wang, Yuxin Shi, Yonglin Lv, Yanjia Hu, Jing Li, Desheng Xiao, Shuang Liu, Qianming Chen, Yongguang Tao\",\"doi\":\"10.1038/s41368-024-00302-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.</p>\",\"PeriodicalId\":14191,\"journal\":{\"name\":\"International Journal of Oral Science\",\"volume\":\"16 1\",\"pages\":\"48\"},\"PeriodicalIF\":10.8000,\"publicationDate\":\"2024-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187069/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Oral Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41368-024-00302-2\",\"RegionNum\":1,\"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":"International Journal of Oral Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41368-024-00302-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0

摘要

口腔黏膜下纤维化(OSF)是一种由咀嚼槟榔引起的慢性炎症性黏膜疾病,属于口腔潜在恶性疾病。成纤维细胞分化异常导致胶原代谢紊乱是口腔黏膜下纤维化发生的核心过程。上皮是抵御外界环境的第一道防线,可以将外界信号转化为病理信号,并参与纤维化微环境的重塑。然而,上皮细胞驱动成纤维细胞分化的具体机制仍不清楚。在这项研究中,我们发现暴露于甲状腺素的上皮细胞通过分泌外泌体与纤维化微环境进行交流。MiR-17-5p 被包裹在上皮细胞衍生的外泌体中,并被成纤维细胞吸收,促进了细胞分泌、收缩、迁移和纤维化标志物(α-SMA 和 I 型胶原)的表达。其潜在的分子机制涉及 miR-17-5p 靶向 Smad7 并通过 E3 泛素化连接酶 WWP1 抑制 TGF-β 受体 1(TGFBR1)的降解,从而促进下游 TGF-β 通路信号的传递。用miR-17-5p抑制剂处理成纤维细胞可逆转上皮源性外泌体诱导的收缩和迁移表型。外泌体 miR-17-5p 被证实是成纤维细胞表型转化的关键调节因子。总之,我们证明了阿雷科林会引发上皮细胞-成纤维细胞的异常串联,并发现上皮细胞衍生的miR-17-5p通过经典的TGF-β纤维化途径介导成纤维细胞分化,这为OSF的诊断和治疗提供了新的视角和策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis.

Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
期刊最新文献
Cuproptosis-related lncRNA JPX regulates malignant cell behavior and epithelial-immune interaction in head and neck squamous cell carcinoma via miR-193b-3p/PLAU axis Correction: An unexpected role of Nogo-A as regulator of tooth enamel formation. Organoids in the oral and maxillofacial region: present and future. Personalized bioceramic grafts for craniomaxillofacial bone regeneration An unexpected role of neurite outgrowth inhibitor A as regulator of tooth enamel formation
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1