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Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis

BACKGROUND: Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a v...

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Autores principales: Qi, Wenchuan, Li, Xiang, Ren, Yanrong, Liu, Xueying, Fu, Hongjuan, Wang, Xiao, Li, Xiao, Xiong, Jian, Zheng, Qianhua, Cai, Dingjun, Liang, Fanrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112552/
https://www.ncbi.nlm.nih.gov/pubmed/35578250
http://dx.doi.org/10.1186/s13020-022-00615-6
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author Qi, Wenchuan
Li, Xiang
Ren, Yanrong
Liu, Xueying
Fu, Hongjuan
Wang, Xiao
Li, Xiao
Xiong, Jian
Zheng, Qianhua
Cai, Dingjun
Liang, Fanrong
author_facet Qi, Wenchuan
Li, Xiang
Ren, Yanrong
Liu, Xueying
Fu, Hongjuan
Wang, Xiao
Li, Xiao
Xiong, Jian
Zheng, Qianhua
Cai, Dingjun
Liang, Fanrong
author_sort Qi, Wenchuan
collection PubMed
description BACKGROUND: Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported. METHODS: In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin–eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG–RXRA complex and promotion of the TGF-β1 transcription. RESULTS: Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3ʹUTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG–RXRA complex and then promote the transcription of TGF-β1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-β1 and inhibiting myocardial fibrosis. CONCLUSION: We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-022-00615-6.
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spelling pubmed-91125522022-05-18 Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis Qi, Wenchuan Li, Xiang Ren, Yanrong Liu, Xueying Fu, Hongjuan Wang, Xiao Li, Xiao Xiong, Jian Zheng, Qianhua Cai, Dingjun Liang, Fanrong Chin Med Research BACKGROUND: Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported. METHODS: In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin–eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG–RXRA complex and promotion of the TGF-β1 transcription. RESULTS: Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3ʹUTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG–RXRA complex and then promote the transcription of TGF-β1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-β1 and inhibiting myocardial fibrosis. CONCLUSION: We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-022-00615-6. BioMed Central 2022-05-17 /pmc/articles/PMC9112552/ /pubmed/35578250 http://dx.doi.org/10.1186/s13020-022-00615-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Qi, Wenchuan
Li, Xiang
Ren, Yanrong
Liu, Xueying
Fu, Hongjuan
Wang, Xiao
Li, Xiao
Xiong, Jian
Zheng, Qianhua
Cai, Dingjun
Liang, Fanrong
Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
title Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
title_full Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
title_fullStr Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
title_full_unstemmed Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
title_short Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
title_sort downregulation of lncrna miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112552/
https://www.ncbi.nlm.nih.gov/pubmed/35578250
http://dx.doi.org/10.1186/s13020-022-00615-6
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