Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation
Objective(s): Atrial fibrillation (AF) is a prevalent arrhythmia accompanied by structural and electrical remodeling of the heart. Here, we examined the possible mechanisms behind the protective role of adipose-derived stem cell (ADSC)-derived exosomes in AF therapy.Materials and Methods: We isolate...
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Mashhad University of Medical Sciences
2025-09-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_25951_de6cf63780fa12f8740dee3e64c4b5cd.pdf |
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| author | Chunpu Li Jiuting Tan Xintao Deng |
| author_facet | Chunpu Li Jiuting Tan Xintao Deng |
| author_sort | Chunpu Li |
| collection | DOAJ |
| description | Objective(s): Atrial fibrillation (AF) is a prevalent arrhythmia accompanied by structural and electrical remodeling of the heart. Here, we examined the possible mechanisms behind the protective role of adipose-derived stem cell (ADSC)-derived exosomes in AF therapy.Materials and Methods: We isolated exosomes from ADSCs. Exosome treatment was given. The left atrial diameter was measured by echocardiographic imaging. Cardiac fibrosis and damage were detected. The interaction between miR-338-3p with circFryl and tissue inhibitor of metalloproteinase mRNA (4TIMP4 mRNA) was predicted and investigated using qPCR and western blotting assay. Results: The overexpression of circFryl in ADSCs elevated the level of circFryl in exosomes and the myocytes, whereas knockdown of circFryl exhibited the opposite effects. Treatment with ADSC-exosomes significantly elevated circFryl level and recovered left atrial diameter, whereas knockdown of circFryl in exosomes abolished these effects. ADSC-exosomes alleviated the cardiac fibrosis and cell apoptosis in the AF model, and the knockdown of circFryl abolished these effects. ADSC-exosomes treatment suppressed viability and fibrosis and enhanced cell apoptosis in Ang-II-induced fibroblasts, which was reversed by depletion of circFryl. Online analysis of miRNA interaction targets showed potential binding between miR-338-3p with circFryl and TIMP4 mRNA. Knockdown of circFryl notably suppressed TIMP4 level, and inhibition of miR-338-3p recovered TIMP4 level. TIMP4 overexpression and miR-338-3p inhibition abolished the effects of sicircFryl in vitro and in vivo. Conclusion: The ADSC-derived exosomes delivered circFryl to interact with miR-338-3p, subsequently enhancing TIMP4 mRNA stability and expression in cardiac fibroblasts and myocytes. The circFryl/miR-338-3p/TIMP4 axis mediated the protective effects of ADSC on AF. |
| format | Article |
| id | doaj-art-b65725dabd6246ba99bcdbdfe19a4f2f |
| institution | DOAJ |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-b65725dabd6246ba99bcdbdfe19a4f2f2025-08-20T02:48:09ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-09-012891180118910.22038/ijbms.2025.84766.1834125951Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillationChunpu Li0Jiuting Tan1Xintao Deng2Department of Cardiology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu 225700, ChinaDepartment of Cardiology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu 225700, ChinaDepartment of Cardiology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu 225700, ChinaObjective(s): Atrial fibrillation (AF) is a prevalent arrhythmia accompanied by structural and electrical remodeling of the heart. Here, we examined the possible mechanisms behind the protective role of adipose-derived stem cell (ADSC)-derived exosomes in AF therapy.Materials and Methods: We isolated exosomes from ADSCs. Exosome treatment was given. The left atrial diameter was measured by echocardiographic imaging. Cardiac fibrosis and damage were detected. The interaction between miR-338-3p with circFryl and tissue inhibitor of metalloproteinase mRNA (4TIMP4 mRNA) was predicted and investigated using qPCR and western blotting assay. Results: The overexpression of circFryl in ADSCs elevated the level of circFryl in exosomes and the myocytes, whereas knockdown of circFryl exhibited the opposite effects. Treatment with ADSC-exosomes significantly elevated circFryl level and recovered left atrial diameter, whereas knockdown of circFryl in exosomes abolished these effects. ADSC-exosomes alleviated the cardiac fibrosis and cell apoptosis in the AF model, and the knockdown of circFryl abolished these effects. ADSC-exosomes treatment suppressed viability and fibrosis and enhanced cell apoptosis in Ang-II-induced fibroblasts, which was reversed by depletion of circFryl. Online analysis of miRNA interaction targets showed potential binding between miR-338-3p with circFryl and TIMP4 mRNA. Knockdown of circFryl notably suppressed TIMP4 level, and inhibition of miR-338-3p recovered TIMP4 level. TIMP4 overexpression and miR-338-3p inhibition abolished the effects of sicircFryl in vitro and in vivo. Conclusion: The ADSC-derived exosomes delivered circFryl to interact with miR-338-3p, subsequently enhancing TIMP4 mRNA stability and expression in cardiac fibroblasts and myocytes. The circFryl/miR-338-3p/TIMP4 axis mediated the protective effects of ADSC on AF.https://ijbms.mums.ac.ir/article_25951_de6cf63780fa12f8740dee3e64c4b5cd.pdfatrial fibrillationexosomesmesenchymal stem cellsmicrornastissue inhibitor of metalloproteinase-4 |
| spellingShingle | Chunpu Li Jiuting Tan Xintao Deng Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation Iranian Journal of Basic Medical Sciences atrial fibrillation exosomes mesenchymal stem cells micrornas tissue inhibitor of metalloproteinase-4 |
| title | Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation |
| title_full | Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation |
| title_fullStr | Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation |
| title_full_unstemmed | Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation |
| title_short | Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation |
| title_sort | adipose stem cell derived exosomes circular rna circfryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation |
| topic | atrial fibrillation exosomes mesenchymal stem cells micrornas tissue inhibitor of metalloproteinase-4 |
| url | https://ijbms.mums.ac.ir/article_25951_de6cf63780fa12f8740dee3e64c4b5cd.pdf |
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