Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 권기환 | * |
dc.date.accessioned | 2021-08-05T16:31:12Z | - |
dc.date.available | 2021-08-05T16:31:12Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 1422-0067 | * |
dc.identifier.other | OAK-29658 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/258489 | - |
dc.description.abstract | Cardiotoxicity is associated with the long-term clinical application of doxorubicin (DOX) in cancer patients. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) including exosomes have been suggested for the treatment of various diseases, including ischemic diseases. However, the effects and functional mechanism of MSC-sEVs in DOX-induced cardiomyopathy have not been clarified. Here, MSC-sEVs were isolated from murine embryonic mesenchymal progenitor cell (C3H/10T1/2) culture media, using ultrafiltration. H9c2 cardiac myoblast cells were pretreated with MSC-sEVs and then exposed to DOX. For in vivo studies, male C57BL/6 mice were administered MSC-sEVs intravenously, prior to a single dose of DOX (15 mg/kg, intraperitoneal). The mice were sacrificed 14 days after DOX treatment. The results showed that MSC-sEVs protected cardiomyocytes from DOX-induced cell death. H9c2 cells treated with DOX showed downregulation of both phosphorylated Akt and survivin, whereas the treatment of MSC-sEVs recovered expression, indicating their anti-apoptotic effects. Three microRNAs (miRNAs) (miR 199a-3p, miR 424-5p, and miR 21-5p) in MSC-sEVs regulated the Akt-Sp1/p53 signaling pathway in cardiomyocytes. Among them, miR 199a-3p was involved in regulating survivin expression, which correlated with the anti-apoptotic effects of MSC-sEVs. In in vivo studies, the echocardiographic results showed that the group treated with MSC-sEVs recovered from DOX-induced cardiomyopathy, showing improvement of both the left ventricle fraction and ejection fraction. MSC-sEVs treatment also increased both survivin and B-cell lymphoma 2 expression in heart tissue compared to the DOX group. Our results demonstrate that MSC-sEVs have protective effects against DOX-induced cardiomyopathy by upregulating survivin expression, which is mediated by the regulation of Akt activation by miRNAs in MSC-sEVs. Thus, MSC-sEVs may be a novel therapy for the prevention of DOX-induced cardiomyopathy. | * |
dc.language | English | * |
dc.publisher | MDPI | * |
dc.subject | MSC-sEVs | * |
dc.subject | doxorubicin-induced cardiomyopathy | * |
dc.subject | survivin | * |
dc.subject | miRNA | * |
dc.subject | apoptosis | * |
dc.title | Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Protect Cardiomyocytes from Doxorubicin-Induced Cardiomyopathy by Upregulating Survivin Expression via the miR-199a-3p-Akt-Sp1/p53 Signaling Pathway | * |
dc.type | Article | * |
dc.relation.issue | 13 | * |
dc.relation.volume | 22 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | * |
dc.identifier.doi | 10.3390/ijms22137102 | * |
dc.identifier.wosid | WOS:000670914000001 | * |
dc.author.google | Lee, Ji Yoon | * |
dc.author.google | Chung, Jihwa | * |
dc.author.google | Byun, Yeongju | * |
dc.author.google | Kim, Kyoung Hwa | * |
dc.author.google | An, Shung Hyun | * |
dc.author.google | Kwon, Kihwan | * |
dc.contributor.scopusid | 권기환(57203037966) | * |
dc.date.modifydate | 20240118164632 | * |