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miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts
BACKGROUND: Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structur...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733651/ https://www.ncbi.nlm.nih.gov/pubmed/33354435 http://dx.doi.org/10.7717/peerj.10502 |
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author | Guo, Huan Zhao, Xinke Su, Haixiang Ma, Chengxu Liu, Kai Kong, Shanshan Liu, Kedan Li, Haining Chang, Juan Wang, Tao Guo, Hongyun Wei, Huiping Fu, Zhaoyuan Lv, Xinfang Li, Yingdong |
author_facet | Guo, Huan Zhao, Xinke Su, Haixiang Ma, Chengxu Liu, Kai Kong, Shanshan Liu, Kedan Li, Haining Chang, Juan Wang, Tao Guo, Hongyun Wei, Huiping Fu, Zhaoyuan Lv, Xinfang Li, Yingdong |
author_sort | Guo, Huan |
collection | PubMed |
description | BACKGROUND: Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structure and function, myocardial fibrosis, the molecular mechanism behind this damage is not well understood. miR-21, a small microRNA, promotes the activation of CFs, leading to cardiac fibrosis. miR-21 is overexpressed after irradiation; however, the relationship between increased miR-21 and myocardial fibrosis after irradiation is unclear. This study was conducted to investigate gene expression after radiation-induced CF damage and the role of miR-21 in this process in rats. METHODS: We sequenced irradiated rat CFs and performed weighted correlation network analysis (WGCNA) combined with differentially expressed gene (DEG) analysis to observe the effect on the expression profile of CF genes after radiation. RESULTS: DEG analysis showed that the degree of gene changes increased with the radiation dose. WGCNA revealed three module eigengenes (MEs) associated with 8.5-Gy-radiation—the Yellow, Brown, Blue modules. The three module eigengenes were related to apoptosis, G2/M phase, and cell death and S phase, respectively. By blocking with the cardiac fibrosis miRNA miR-21, we found that miR-21 was associated with G2/M blockade in the cell cycle and was mainly involved in regulating extracellular matrix-related genes, including Grem1, Clu, Gdf15, Ccl7, and Cxcl1. Stem-loop quantitative real-time PCR was performed to verify the expression of these genes. Five genes showed higher expression after 8.5 Gy-radiation in CFs. The target genes of miR-21 predicted online were Gdf15 and Rsad2, which showed much higher expression after treatment with antagomir-miR-21 in 8.5-Gy-irradiated CFs. Thus, miR-21 may play the role of fibrosis and G2/M blockade in regulating Grem1, Clu, Gdf15, Ccl7, Cxcl1, and Rsad2 post-irradiation. |
format | Online Article Text |
id | pubmed-7733651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77336512020-12-21 miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts Guo, Huan Zhao, Xinke Su, Haixiang Ma, Chengxu Liu, Kai Kong, Shanshan Liu, Kedan Li, Haining Chang, Juan Wang, Tao Guo, Hongyun Wei, Huiping Fu, Zhaoyuan Lv, Xinfang Li, Yingdong PeerJ Bioinformatics BACKGROUND: Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structure and function, myocardial fibrosis, the molecular mechanism behind this damage is not well understood. miR-21, a small microRNA, promotes the activation of CFs, leading to cardiac fibrosis. miR-21 is overexpressed after irradiation; however, the relationship between increased miR-21 and myocardial fibrosis after irradiation is unclear. This study was conducted to investigate gene expression after radiation-induced CF damage and the role of miR-21 in this process in rats. METHODS: We sequenced irradiated rat CFs and performed weighted correlation network analysis (WGCNA) combined with differentially expressed gene (DEG) analysis to observe the effect on the expression profile of CF genes after radiation. RESULTS: DEG analysis showed that the degree of gene changes increased with the radiation dose. WGCNA revealed three module eigengenes (MEs) associated with 8.5-Gy-radiation—the Yellow, Brown, Blue modules. The three module eigengenes were related to apoptosis, G2/M phase, and cell death and S phase, respectively. By blocking with the cardiac fibrosis miRNA miR-21, we found that miR-21 was associated with G2/M blockade in the cell cycle and was mainly involved in regulating extracellular matrix-related genes, including Grem1, Clu, Gdf15, Ccl7, and Cxcl1. Stem-loop quantitative real-time PCR was performed to verify the expression of these genes. Five genes showed higher expression after 8.5 Gy-radiation in CFs. The target genes of miR-21 predicted online were Gdf15 and Rsad2, which showed much higher expression after treatment with antagomir-miR-21 in 8.5-Gy-irradiated CFs. Thus, miR-21 may play the role of fibrosis and G2/M blockade in regulating Grem1, Clu, Gdf15, Ccl7, Cxcl1, and Rsad2 post-irradiation. PeerJ Inc. 2020-12-10 /pmc/articles/PMC7733651/ /pubmed/33354435 http://dx.doi.org/10.7717/peerj.10502 Text en ©2020 Guo et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Guo, Huan Zhao, Xinke Su, Haixiang Ma, Chengxu Liu, Kai Kong, Shanshan Liu, Kedan Li, Haining Chang, Juan Wang, Tao Guo, Hongyun Wei, Huiping Fu, Zhaoyuan Lv, Xinfang Li, Yingdong miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts |
title | miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts |
title_full | miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts |
title_fullStr | miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts |
title_full_unstemmed | miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts |
title_short | miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts |
title_sort | mir-21 is upregulated, promoting fibrosis and blocking g2/m in irradiated rat cardiac fibroblasts |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733651/ https://www.ncbi.nlm.nih.gov/pubmed/33354435 http://dx.doi.org/10.7717/peerj.10502 |
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