文献类型：期刊文献

英文题名：miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts

作者：Guo, Huan[1,2,3];Zhao, Xinke[4,5];Su, Haixiang[3];Ma, Chengxu[6];Liu, Kai[2];Kong, Shanshan[2];Liu, Kedan[3];Li, Haining[3];Chang, Juan[2];Wang, Tao[3];Guo, Hongyun[3];Wei, Huiping[4];Fu, Zhaoyuan[4];Lv, Xinfang[3];Li, Yingdong[1,2]

第一作者：Guo, Huan;郭华

通信作者：Li, YD[1];Li, YD[2]

机构：[1]Lan Zhou Univ, Sch Basic Med Sci, Lanzhou, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China;[3]Gansu Prov Canc Hosp, Gansu Prov Acad Inst Med Sci, Lanzhou, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Dept Intervent Sect, Affiliated Hosp, Lanzhou, Gansu, Peoples R China;[5]Chinese Acad Med Sci, Fuwai Hosp, Beijing, Peoples R China;[6]Lanzhou Univ, Dept Endocrinol, Hosp 1, Lanzhou, Gansu, Peoples R China

第一机构：Lan Zhou Univ, Sch Basic Med Sci, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Lan Zhou Univ, Sch Basic Med Sci, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2020

卷号：8

外文期刊名：PEERJ

收录：;Scopus(收录号：2-s2.0-85097621895);WOS:【SCI-EXPANDED(收录号:WOS:000597121100004)】；

基金：This work was supported by the National Natural Science Foundation of China [grant numbers: 81760798, 81873132, (Yingdong Li) and 81860786 (Xin Ke Zhao)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

外文关键词：Heart; CFs; X-ray; WGCNA and DEG; Fibrosis; Cell cycle

摘要：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 Grem 1, Clu, Gdf15, Cc17, Cxcl1, and Rsad2 post-irradiation.