CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction.
Yan Wang,Chaofu Li,Ranzun Zhao,Zhimei Qiu,Changyin Shen,Zhenglong Wang,Weiwei Liu,Wei Zhang,Junbo Ge,Bei Shi +9 more
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In this paper, the role of circular RNAs (circRNAs) in M2 macrophage (M2M)-derived small extracellular vesicles (SEVs) in myocardial fibrosis development was explored.Abstract:
Objective: This study aimed to explore the role of circular RNAs (circRNAs) in M2 macrophage (M2M)-derived small extracellular vesicles (SEVs) in myocardial fibrosis development. Methods: The regulatory role of M2M-derived extracellular vesicles (EVs) was evaluated in a mouse model of acute myocardial infarction. Immunofluorescence, quantitative real-time PCR (RT-qPCR), nanoparticle tracking analysis, Western blot analysis and electron microscopy were used to identify macrophages, large extracellular vesicles (LEVs) and SEVs. The circRNA expression profiles of M0 macrophages (M0Ms) and M2Ms were determined by microarray analysis. Bioinformatic analysis, cell coculture and cell proliferation assays were performed to investigate the expression, function, and regulatory mechanisms of circUbe3a in vitro. qPCR, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, RNA fluorescence in situ hybridization (RNA-FISH), Western blot analysis and a series of rescue experiments were used to verify the correlation among circUbe3a, miR-138-5p and RhoC. Results: CircUbe3a from M2M-derived SEVs triggered functional changes in cardiac fibroblasts (CFs). CircUbe3a was synthesized and loaded into SEVs during increased M2M infiltration after myocardial infarction. The fusion of the released SEVs with the plasma membrane likely caused the release of circUbe3a into the cytosol of CFs. Silencing or overexpressing circUbe3a altered CF proliferation, migration, and phenotypic transformation in vitro. We confirmed that circUbe3a plays a crucial role in enhancing functional changes in CFs by sponging miR-138-5p and then translationally repressing RhoC in vitro. In vivo, the addition of M2M-derived SEVs or overexpression of circUbe3a significantly exacerbated myocardial fibrosis after acute myocardial infarction, and these effects were partially abolished by circUbe3a-specific shRNA. Conclusions: Our findings suggest that M2M-derived circUbe3a-containing SEVs promote the proliferation, migration, and phenotypic transformation of CFs by directly targeting the miR-138-5p/RhoC axis, which may also exacerbate myocardial fibrosis after acute myocardial infarction.read more
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Emerging roles of circRNAs in the pathological process of myocardial infarction
TL;DR: In this paper, a review summarizes the pathophysiological process of myocardial infarction and various approaches to measure circRNA levels in MI patients, tissues, and cells; highlights the significance of circRNAs in the regulation MI pathogenesis and development; and provides potential clinical insight for the diagnosis, prognosis, and treatment of MI.
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Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications
TL;DR: In this article , the authors summarize the findings from recent research on the biological functions of EVs in the ischemic heart disease and heart failure, and their potential as novel diagnostic biomarkers and therapeutic opportunities.
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Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.
TL;DR: In this article, the authors summarize the findings from recent research on the biological functions of EVs in the ischemic heart disease and heart failure, and their potential as novel diagnostic biomarkers and therapeutic opportunities.
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Extracellular Vesicles, Inflammation, and Cardiovascular Disease
TL;DR: The mechanistic role of extracellular vesicles at the intersection of inflammatory processes and cardiovascular disease is described, which focuses on atherosclerosis, myocardial ischemia and ischemic heart disease, heart failure, aortic aneurysms, and valvular pathology.
Journal ArticleDOI
hnRNPL-activated circANKRD42 back-splicing and circANKRD42-mediated crosstalk of mechanical stiffness and biochemical signal in lung fibrosis
Pan Xu,Jinjin Zhang,Meirong Wang,Bo Liu,Rongrong Li,Hongbo Li,Nailiang Zhai,Weili Liu,Changjun Lv,Xiaodong Song +9 more
TL;DR: In this paper , a novel circRNA-ankyrin repeat domain 42 (ANKRD42) from peripheral blood of patients with IPF, which participated in pulmonary fibrosis through the close communication of mechanical stiffness and biochemical signals, was identified.
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TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Journal ArticleDOI
The biogenesis, biology and characterization of circular RNAs.
Lasse Sommer Kristensen,Maria S. Andersen,Lotte V. W. Stagsted,Karoline K. Ebbesen,Thomas B. Hansen,Jørgen Kjems +5 more
TL;DR: Advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
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Exon-intron circular RNAs regulate transcription in the nucleus
Zhaoyong Li,Chuan Huang,Chun Bao,Liang Chen,Mei Lin,Xiaolin Wang,Guolin Zhong,Bin Yu,Wanchen Hu,Limin Dai,Pengfei Zhu,Zhaoxia Chang,Qingfa Wu,Yi Zhao,Ya Jia,Ping Xu,Huijie Liu,Ge Shan +17 more
TL;DR: A new role for circRNAs in regulating gene expression in the nucleus is revealed, in which EIciRNAs enhance the expression of their parental genes in cis, and a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EICIRNAs is highlighted.
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Circular Intronic Long Noncoding RNAs
Yang Zhang,Xiao-Ou Zhang,Tian Chen,Jian-Feng Xiang,Qing-Fei Yin,Yu-Hang Xing,Shanshan Zhu,Li Yang,Ling-Ling Chen +8 more
TL;DR: A cis-regulatory role of noncoding intronic transcripts on their parent coding genes is suggested, which largely accumulates to its sites of transcription, associates with elongation Pol II machinery, and acts as a positive regulator of Pol II transcription.
Journal ArticleDOI
CircRNA: functions and properties of a novel potential biomarker for cancer
Meng Shujuan,Meng Shujuan,Zhou Hecheng,Zhou Hecheng,Feng Ziyang,Feng Ziyang,Xu Zihao,Xu Zihao,Tang Ying,Tang Ying,Peiyao Li,Minghua Wu +11 more
TL;DR: A review of recent research shows that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours.