Adipose-Derived Mesenchymal Stem Cells-Derived Exosomes Carry MicroRNA-671 to Alleviate Myocardial Infarction Through Inactivating the TGFBR2/Smad2 Axis
| Autor: | Qing Yang, Yuhai Zhu, Chengcheng Wu, Wennan Liu, Xue Wang, Yujie He |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
microRNA-671 Immunology Myocardial Infarction Inflammation Mice Transgenic Smad2 Protein exosomes 030204 cardiovascular system & hematology Mesenchymal Stem Cell Transplantation MSC 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation In vivo medicine Immunology and Allergy Animals Myocytes Cardiac Cells Cultured biology Chemistry Mesenchymal stem cell Receptor Transforming Growth Factor-beta Type II Mesenchymal Stem Cells Transforming growth factor beta In vitro Microvesicles Cell Hypoxia Cell biology TGFBR2 carbohydrates (lipids) Mice Inbred C57BL MicroRNAs 030104 developmental biology Glucose biology.protein Myocardial fibrosis Original Article medicine.symptom Smad2 |
| Zdroj: | Inflammation |
| ISSN: | 1573-2576 |
| Popis: | Abstract Mesenchymal stem cells (MSCs) and their derived extracellular vesicles have been reported as promising tools for the management of heart disease. The aim of this study was to explore the function of adipose-derived MSCs (adMSCs)-derived exosomes (Exo) in the progression of myocardial infarction (MI) and the molecules involved. Mouse cardiomyocytes were treated with oxygen-glucose deprivation (OGD) to mimic an MI condition in vitro. The adMSCs-derived Exo were identified and administrated into the OGD-treated cardiomyocytes, and then the viability and apoptosis of cells, and the secretion of fibrosis- and inflammation-related cytokines in cells were determined. Differentially expressed microRNAs (miRNAs) in cells after Exo treatment were screened using a microarray analysis. The downstream molecules regulated by miR-671 were explored through bioinformatic analysis. Involvements of miR-671 and transforming growth factor beta receptor 2 (TGFBR2) in the exosome-mediated events were confirmed by rescue experiments. A murine model with MI was induced and treated with Exo for functional experiments in vivo. Compared to phosphate-buffered saline treatment, the Exo treatment significantly enhanced viability while reduced apoptosis of cardiomyocytes, and in reduced myocardial fibrosis and inflammation both in vitro and in vivo. miR-671 was significantly upregulated in cells after Exo treatment. Downregulation of miR-671 blocked the protective functions of Exo. miR-671 targeted TGFBR2 and suppressed phosphorylation of Smad2. Artificial downregulation of TGFBR2 enhanced viability of the OGD-treated cardiomyocytes. This study suggested that adMSC-derived exosomal miR-671 directly targets TGFBR2 and reduces Smad2 phosphorylation to alleviate MI-like symptoms both in vivo and in vitro. |
| Databáze: | OpenAIRE |
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