下调miR-761通过调节PGC-1α改善辐射诱导的肺纤维化。

IF 1.5 4区 医学 Q3 RESPIRATORY SYSTEM
Experimental Lung Research Pub Date : 2022-04-01 Epub Date: 2022-07-29 DOI:10.1080/01902148.2022.2104407
Zeng Wang, Junying Chen, Li Su, Jinsheng Hong
{"title":"下调miR-761通过调节PGC-1α改善辐射诱导的肺纤维化。","authors":"Zeng Wang,&nbsp;Junying Chen,&nbsp;Li Su,&nbsp;Jinsheng Hong","doi":"10.1080/01902148.2022.2104407","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Radiation-induced pulmonary fibrosis (RIPF) is a serious complication in patients treated with transthoracic irradiation. To date, there are no effective drugs for RIPF treatment. In this study, we attempted to explore the function of miR-761 in RIPF, further investigate its potential mechanism and evaluate its effectiveness in the treatment of RIPF. <b>Methods:</b> qRT-PCR analysis was used to detect miR-761 and peroxisome proliferator-activated receptor gamma (PPARg) coactivator-1 (PGC-1α) expression. Western Blot (WB) assay was applied to verify the regulation of PGC-1α by miR-761 and the expression of fibrosis-related proteins. Gel contraction assay was performed to demonstrate the level of fibroblast activation in vitro. A mouse RIPF model was used to validate the anti-fibrotic effect of Antagomir761. Bioinformatics analysis and dual-luciferase reporter assays were utilized to confirm the regulation relationship between miR-761 and PGC-1α. <b>Results:</b> The results showed that miR-761 was significantly elevated in irradiated mice lungs and fibroblasts. Overexpression of miR-761 in vitro promoted fibroblast activation. Whereas inhibition of miR-761 attenuated the degree of RIPF and inhibited fibroblast activation. Mechanistically, PGC-1α was a direct and functional target of miR-761, overexpression of PGC-1α inhibited irradiation-induced fibroblast activation, and knockdown of PGC-1α caused miR-761 inhibitor loses its anti-activation ability in irradiated cells. <b>Conclusion:</b> Our findings demonstrated that miR-761 regulated RIPF by targeting PGC-1α. Inhibition of miR-761 restored PGC-1α expression and attenuated RIPF damage, and miR-761 was a potential target for preventing the development of RIPF.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"158-167"},"PeriodicalIF":1.5000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Downregulation of miR-761 ameliorates radiation-induced pulmonary fibrosis by regulating PGC-1α.\",\"authors\":\"Zeng Wang,&nbsp;Junying Chen,&nbsp;Li Su,&nbsp;Jinsheng Hong\",\"doi\":\"10.1080/01902148.2022.2104407\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> Radiation-induced pulmonary fibrosis (RIPF) is a serious complication in patients treated with transthoracic irradiation. To date, there are no effective drugs for RIPF treatment. In this study, we attempted to explore the function of miR-761 in RIPF, further investigate its potential mechanism and evaluate its effectiveness in the treatment of RIPF. <b>Methods:</b> qRT-PCR analysis was used to detect miR-761 and peroxisome proliferator-activated receptor gamma (PPARg) coactivator-1 (PGC-1α) expression. Western Blot (WB) assay was applied to verify the regulation of PGC-1α by miR-761 and the expression of fibrosis-related proteins. Gel contraction assay was performed to demonstrate the level of fibroblast activation in vitro. A mouse RIPF model was used to validate the anti-fibrotic effect of Antagomir761. Bioinformatics analysis and dual-luciferase reporter assays were utilized to confirm the regulation relationship between miR-761 and PGC-1α. <b>Results:</b> The results showed that miR-761 was significantly elevated in irradiated mice lungs and fibroblasts. Overexpression of miR-761 in vitro promoted fibroblast activation. Whereas inhibition of miR-761 attenuated the degree of RIPF and inhibited fibroblast activation. Mechanistically, PGC-1α was a direct and functional target of miR-761, overexpression of PGC-1α inhibited irradiation-induced fibroblast activation, and knockdown of PGC-1α caused miR-761 inhibitor loses its anti-activation ability in irradiated cells. <b>Conclusion:</b> Our findings demonstrated that miR-761 regulated RIPF by targeting PGC-1α. Inhibition of miR-761 restored PGC-1α expression and attenuated RIPF damage, and miR-761 was a potential target for preventing the development of RIPF.</p>\",\"PeriodicalId\":12206,\"journal\":{\"name\":\"Experimental Lung Research\",\"volume\":\" \",\"pages\":\"158-167\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2022-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Lung Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/01902148.2022.2104407\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/7/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Lung Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01902148.2022.2104407","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/7/29 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0

摘要

背景:放射诱导肺纤维化(RIPF)是经胸放射治疗患者的严重并发症。迄今为止,还没有有效的RIPF治疗药物。在本研究中,我们试图探索miR-761在RIPF中的功能,进一步探讨其潜在机制,并评估其治疗RIPF的有效性。方法:采用qRT-PCR检测miR-761和过氧化物酶体增殖物激活受体γ (ppar)共激活因子-1 (PGC-1α)的表达。Western Blot (WB)检测miR-761对PGC-1α的调控及纤维化相关蛋白的表达。凝胶收缩实验显示成纤维细胞在体外的活化水平。采用小鼠RIPF模型验证Antagomir761的抗纤维化作用。利用生物信息学分析和双荧光素酶报告基因检测来证实miR-761与PGC-1α之间的调控关系。结果:结果显示,miR-761在辐照小鼠肺和成纤维细胞中显著升高。在体外过表达miR-761促进成纤维细胞活化。而抑制miR-761则减弱了RIPF的程度并抑制了成纤维细胞的活化。在机制上,PGC-1α是miR-761的直接和功能靶点,PGC-1α的过表达抑制辐照诱导的成纤维细胞活化,PGC-1α的敲低导致miR-761抑制剂在辐照细胞中失去抗活化能力。结论:我们的研究结果表明miR-761通过靶向PGC-1α调控RIPF。抑制miR-761可恢复PGC-1α表达并减轻RIPF损伤,miR-761是阻止RIPF发展的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Downregulation of miR-761 ameliorates radiation-induced pulmonary fibrosis by regulating PGC-1α.

Background: Radiation-induced pulmonary fibrosis (RIPF) is a serious complication in patients treated with transthoracic irradiation. To date, there are no effective drugs for RIPF treatment. In this study, we attempted to explore the function of miR-761 in RIPF, further investigate its potential mechanism and evaluate its effectiveness in the treatment of RIPF. Methods: qRT-PCR analysis was used to detect miR-761 and peroxisome proliferator-activated receptor gamma (PPARg) coactivator-1 (PGC-1α) expression. Western Blot (WB) assay was applied to verify the regulation of PGC-1α by miR-761 and the expression of fibrosis-related proteins. Gel contraction assay was performed to demonstrate the level of fibroblast activation in vitro. A mouse RIPF model was used to validate the anti-fibrotic effect of Antagomir761. Bioinformatics analysis and dual-luciferase reporter assays were utilized to confirm the regulation relationship between miR-761 and PGC-1α. Results: The results showed that miR-761 was significantly elevated in irradiated mice lungs and fibroblasts. Overexpression of miR-761 in vitro promoted fibroblast activation. Whereas inhibition of miR-761 attenuated the degree of RIPF and inhibited fibroblast activation. Mechanistically, PGC-1α was a direct and functional target of miR-761, overexpression of PGC-1α inhibited irradiation-induced fibroblast activation, and knockdown of PGC-1α caused miR-761 inhibitor loses its anti-activation ability in irradiated cells. Conclusion: Our findings demonstrated that miR-761 regulated RIPF by targeting PGC-1α. Inhibition of miR-761 restored PGC-1α expression and attenuated RIPF damage, and miR-761 was a potential target for preventing the development of RIPF.

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
Experimental Lung Research
Experimental Lung Research 医学-呼吸系统
CiteScore
3.80
自引率
0.00%
发文量
23
审稿时长
2 months
期刊介绍: Experimental Lung Research publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. Emphasis is placed on investigations concerned with molecular, biochemical, and cellular mechanisms of normal function, pathogenesis, and responses to injury. The journal publishes reports on important methodological advances on new experimental modes. Also published are invited reviews on important and timely research advances, as well as proceedings of specialized symposia. Authors can choose to publish gold open access in this journal.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信