PMID- 31924121 OWN - NLM STAT- MEDLINE DCOM- 20201125 LR - 20210422 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 19 IP - 3 DP - 2020 Feb TI - Human umbilical cord mesenchymal stem cells-derived exosomes transfers microRNA-19a to protect cardiomyocytes from acute myocardial infarction by targeting SOX6. PG - 339-353 LID - 10.1080/15384101.2019.1711305 [doi] AB - Exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSCs) protect cardiomyocytes from anoxia-reoxygenation injury. But the mechanism of hucMSC-exo-microRNA (miR)-19a in acute myocardial infarction (AMI) remains unclear. For this study, cardiac function related indicators, inflammatory factors and markers of myocardial injury, cardiomyocyte injury, infarct size, and apoptosis were detected in vivo experiments. The gain-and loss-of function was performed to evaluate the effects of hucMSC-exo with down/upregulated miR-19a on AMI rats and hypoxic H9C2 cells. Western blot analysis was used to detect levels of AKT/JNK3/caspase-3 axis-related proteins. Consequently, hucMSC-exo alleviated AMI and inhibited cardiomyocyte apoptosis. miR-19a was downregulated in AMI tissues and cells, and increased after hucMSC-exo treatment. miR-19a knockdown in hucMSC-exo impaired the protective role of hucMSC-exo alone in the AMI damage. SOX6 is a target gene of miR-19a and its inhibition lightened hypoxic damage of H9C2 cells. SOX6 knockdown together with miR-19a inhibition in hucMSC-exo activated AKT and inhibited JNK3/caspase-3 axis. Taken together, hucMSC-exo protected cardiomyocytes from AMI injury by transferring miR-19a, targeting SOX6, activating AKT, and inhibiting JNK3/caspase-3 activation. This study may provide new understanding for AMI treatment. FAU - Huang, Lin AU - Huang L AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China. FAU - Yang, Lu AU - Yang L AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China. FAU - Ding, Yin AU - Ding Y AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China. FAU - Jiang, Xinghua AU - Jiang X AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China. FAU - Xia, Zhen AU - Xia Z AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China. FAU - You, Zhigang AU - You Z AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200110 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (Cytokines) RN - 0 (MIRN19 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Protective Agents) RN - 0 (Reactive Oxygen Species) RN - 0 (SOX6 protein, human) RN - 0 (SOXD Transcription Factors) RN - EC 2.7.1.- (Mitogen-Activated Protein Kinase 10) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/genetics MH - Caspase 3/metabolism MH - Cell Hypoxia MH - Cell Line MH - Coculture Techniques MH - Cytokines/metabolism MH - Exosomes/genetics/*metabolism/ultrastructure MH - Humans MH - Male MH - Mesenchymal Stem Cells/cytology/*metabolism MH - MicroRNAs/genetics/*metabolism MH - Mitogen-Activated Protein Kinase 10/metabolism MH - Myocardial Infarction/genetics/*metabolism/therapy MH - Myocytes, Cardiac/*metabolism/pathology MH - Protective Agents/pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - SOXD Transcription Factors/genetics/*metabolism MH - Umbilical Cord/cytology/*metabolism PMC - PMC7028160 OTO - NOTNLM OT - AKT/JNK3/caspase-3 axis OT - Acute myocardial infarction OT - Exosomes OT - Human umbilical cord mesenchymal stem cells OT - SOX6 OT - microRNA-19a EDAT- 2020/01/12 06:00 MHDA- 2020/11/26 06:00 PMCR- 2021/01/10 CRDT- 2020/01/12 06:00 PHST- 2020/01/12 06:00 [pubmed] PHST- 2020/11/26 06:00 [medline] PHST- 2020/01/12 06:00 [entrez] PHST- 2021/01/10 00:00 [pmc-release] AID - 1711305 [pii] AID - 10.1080/15384101.2019.1711305 [doi] PST - ppublish SO - Cell Cycle. 2020 Feb;19(3):339-353. doi: 10.1080/15384101.2019.1711305. Epub 2020 Jan 10.