Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1
Background. At present, the study has confirmed that the mesenchymal stem cell-derived exosomes (MCSs-Exo) possess cardio-protection in sepsis. Nevertheless, the molecular mechanism of the protection of MSCs-Exo in sepsis remains unknown. Therefore, this research is aimed at studying the molecular m...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/1530445 |
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| author | Chun Liu Jianhua Xue Bo Xu Aixian Zhang Lili Qin Jiajia Liu Yang Yang |
| author_facet | Chun Liu Jianhua Xue Bo Xu Aixian Zhang Lili Qin Jiajia Liu Yang Yang |
| author_sort | Chun Liu |
| collection | DOAJ |
| description | Background. At present, the study has confirmed that the mesenchymal stem cell-derived exosomes (MCSs-Exo) possess cardio-protection in sepsis. Nevertheless, the molecular mechanism of the protection of MSCs-Exo in sepsis remains unknown. Therefore, this research is aimed at studying the molecular mechanism. Methods. The effects of MSCs-Exo and miR-146a-5p in LPS-induced cardiomyocytes (H9C2 cells) in vitro were verified by CCK-8, EdU assay, flow cytometry, Western blot assay, and RT-qPCR. The effect of MSCs-Exo in vivo was evaluated by CLP-induced sepsis model. The potential gene in MSCs-Exo was verified by bioinformatics analysis, and the potential target of miR-146a-5p was identified by bioinformatics analysis and luciferase reporter assay. At last, the function of miR-146a-5p and its target genes on LPS-induced cardiomyocytes (H9C2 cells) in vitro was validated by recuse experiment. Results. Our findings revealed that MSCs-Exo could effectively protect cardiomyocytes of inflammation model in vitro and myocardial tissues of sepsis model in vivo. Meanwhile, we found that miR-146a-5p was a potential gene in MSCs-Exo, and MYBL1 was the target gene of miR-146a-5p and negatively regulated by miR-146a-5p. In addition, miR-146a-5p overexpression promoted proliferation and inhibited apoptosis of LPS-induced cardiomyocytes. The rescue experiment demonstrated that miR-146a-5p could effectively repress the inflammatory response of cardiomyocytes via decreasing MYBL1 expression. Conclusion. This study suggests that miR-146a-5p-bearing MSC-derived exosomes may become an effective treatment for sepsis. |
| format | Article |
| id | doaj-art-dfbb27b6a6a2431fbbfb1217a1b3fcc6 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-dfbb27b6a6a2431fbbfb1217a1b3fcc62025-08-20T03:26:25ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/15304451530445Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1Chun Liu0Jianhua Xue1Bo Xu2Aixian Zhang3Lili Qin4Jiajia Liu5Yang Yang6Department of Emergency Medicine, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province 226001, ChinaDepartment of Trauma Center, Affiliated Hospital of Nantong University, Nantongy, Jiangsu Province 226001, ChinaDepartment of Orthopaedics, Qidong Hospital of Traditional Chinese Medicine, Nantong City, Jiangsu Province 226200, ChinaDepartment of General Practice Medicine, Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province 226001, ChinaDepartment of Endoscopic Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, ChinaDepartment of Trauma Center, Affiliated Hospital of Nantong University, Nantongy, Jiangsu Province 226001, ChinaDepartment of Trauma Center, Affiliated Hospital of Nantong University, Nantongy, Jiangsu Province 226001, ChinaBackground. At present, the study has confirmed that the mesenchymal stem cell-derived exosomes (MCSs-Exo) possess cardio-protection in sepsis. Nevertheless, the molecular mechanism of the protection of MSCs-Exo in sepsis remains unknown. Therefore, this research is aimed at studying the molecular mechanism. Methods. The effects of MSCs-Exo and miR-146a-5p in LPS-induced cardiomyocytes (H9C2 cells) in vitro were verified by CCK-8, EdU assay, flow cytometry, Western blot assay, and RT-qPCR. The effect of MSCs-Exo in vivo was evaluated by CLP-induced sepsis model. The potential gene in MSCs-Exo was verified by bioinformatics analysis, and the potential target of miR-146a-5p was identified by bioinformatics analysis and luciferase reporter assay. At last, the function of miR-146a-5p and its target genes on LPS-induced cardiomyocytes (H9C2 cells) in vitro was validated by recuse experiment. Results. Our findings revealed that MSCs-Exo could effectively protect cardiomyocytes of inflammation model in vitro and myocardial tissues of sepsis model in vivo. Meanwhile, we found that miR-146a-5p was a potential gene in MSCs-Exo, and MYBL1 was the target gene of miR-146a-5p and negatively regulated by miR-146a-5p. In addition, miR-146a-5p overexpression promoted proliferation and inhibited apoptosis of LPS-induced cardiomyocytes. The rescue experiment demonstrated that miR-146a-5p could effectively repress the inflammatory response of cardiomyocytes via decreasing MYBL1 expression. Conclusion. This study suggests that miR-146a-5p-bearing MSC-derived exosomes may become an effective treatment for sepsis.http://dx.doi.org/10.1155/2021/1530445 |
| spellingShingle | Chun Liu Jianhua Xue Bo Xu Aixian Zhang Lili Qin Jiajia Liu Yang Yang Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1 Stem Cells International |
| title | Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1 |
| title_full | Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1 |
| title_fullStr | Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1 |
| title_full_unstemmed | Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1 |
| title_short | Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1 |
| title_sort | exosomes derived from mir 146a 5p enriched mesenchymal stem cells protect the cardiomyocytes and myocardial tissues in the polymicrobial sepsis through regulating mybl1 |
| url | http://dx.doi.org/10.1155/2021/1530445 |
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