Exosomes Containing LINC00636 Inhibit MAPK1 through the miR-450a-2-3p Overexpression in Human Pericardial Fluid and Improve Cardiac Fibrosis in Patients with Atrial Fibrillation
| Autor: | Kaibo Lei, Fanyan Luo, Langsha Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD31 Blood Platelets Article Subject Cardiac fibrosis Immunology Vimentin 030204 cardiovascular system & hematology Exosomes Umbilical vein 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Atrial Fibrillation Pathology medicine Human Umbilical Vein Endothelial Cells RB1-214 Humans Cell Proliferation Mitogen-Activated Protein Kinase 1 biology business.industry Pericardial fluid Computational Biology Muscle Smooth Cell Biology Fibroblasts medicine.disease Fibrosis Actins Endothelial stem cell MicroRNAs 030104 developmental biology Gene Expression Regulation Cancer research biology.protein Pericardial Fluid Myocardial fibrosis RNA Long Noncoding business Research Article |
| Zdroj: | Mediators of Inflammation Mediators of Inflammation, Vol 2021 (2021) |
| ISSN: | 1466-1861 |
| Popis: | The purpose of this study was to investigate the regulatory mechanism of miR-450a-2-3p in myocardial fibrosis in patients with atrial fibrillation. For this purpose, the expression profile of GSE55296 was extracted from the GEO database, and differentially expressed lncRNAs were identified. Gene ontology analysis of the target genes of mir-450a-2-3p indicated that there was a regulatory relationship between LINC00636 and miR-450a-2-3p. Further, the expression levels of the analyzed RNAs were confirmed by RT-qPCR. TGF-β1-induced cardiac fibroblasts (CFs) and human umbilical vein endothelial cells (HUVECs) were used to establish a myocardial fibrosis model and endothelium-mesenchymal transformation (EMT) model in vivo. We hypothesized that exosomes containing LINC00636 regulate the expression of miR-450a-2-3p. LINC00636 was positively correlated with the expression of miR-450a-2-3p. The overexpression of miR-450a-2-3p suppressed the MAPK1 expression in CFs, thereby inhibiting the expression of α-SMA, COL1, and COL3 and preventing CF proliferation. In HUVECs, the miR-450a-2-3p overexpression upregulated the expression of VE-Cadherin (VE-Cad) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) by inhibiting the mitogen-activated protein kinase 1 (MAPK1) expression, whereas the expression levels of vimentin, COL1, and COL3 decreased. These results indicate that LINC00636, which is present in human pericardial fluid, is an antifibrotic molecule that inhibits MAPK1 through the miR-450a-2-3p overexpression and improves cardiac fibrosis in patients with atrial fibrillation. |
| Databáze: | OpenAIRE |
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