Nicoline W E van den Berg, Makiri Kawasaki, Fransisca A Nariswari, Benedetta Fabrizi, Jolien Neefs, Ingeborg van der Made, Robin Wesselink, Wim Jan P van Boven, Antoine H G Driessen, Aldo Jongejan, Joris R de Groot
{"title":"MicroRNAs in atrial fibrillation target genes in structural remodelling.","authors":"Nicoline W E van den Berg, Makiri Kawasaki, Fransisca A Nariswari, Benedetta Fabrizi, Jolien Neefs, Ingeborg van der Made, Robin Wesselink, Wim Jan P van Boven, Antoine H G Driessen, Aldo Jongejan, Joris R de Groot","doi":"10.1007/s00441-023-03823-0","DOIUrl":null,"url":null,"abstract":"<p><p>We aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA-mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697892/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Tissue Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00441-023-03823-0","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
We aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA-mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.
期刊介绍:
The journal publishes regular articles and reviews in the areas of molecular, cell, and supracellular biology. In particular, the journal intends to provide a forum for publishing data that analyze the supracellular, integrative actions of gene products and their impact on the formation of tissue structure and function. Submission of papers with an emphasis on structure-function relationships as revealed by recombinant molecular technologies is especially encouraged. Areas of research with a long-standing tradition of publishing in Cell & Tissue Research include:
- neurobiology
- neuroendocrinology
- endocrinology
- reproductive biology
- skeletal and immune systems
- development
- stem cells
- muscle biology.