Leiying Zhang1, Qingxia Wei2, Xiaomin Liu3, Ting Zhang4, Shuying Wang5, Lingling Zhou6, Liyang Zou7, Fengyan Fan8, Hongxu Chi9, Jiayi Sun10, Deqing Wang11. 1. Medical School of Chinese PLA, Beijing, China; Department of Blood Transfusion Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address: zhangleiying0312@163.com. 2. Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Chinese PLA General Hospital, Beijing, China. Electronic address: wqxpumc@163.com. 3. Department of Blood Transfusion Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address: xiaominliu88@163.com. 4. Training Division of the Medical Administration Department, the First Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: 1455440750@qq.com. 5. Medical School of Chinese PLA, Beijing, China. Electronic address: 1172371648@qq.com. 6. Department of Blood Transfusion Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address: lingling19870702@163.com. 7. Department of Blood Transfusion Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address: zouliyang823@163.com. 8. Department of Blood Transfusion, Air Force Medical Center, Chinese PLA, Beijing, China. Electronic address: Cpwsf@139.com. 9. Department of Blood Transfusion Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address: liubin102@126.com. 10. Chinese National Human Genome Center, Beijing, China. Electronic address: sunjiayi1231@163.com. 11. Medical School of Chinese PLA, Beijing, China; Department of Blood Transfusion Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address: deqingw@vip.sina.com.
Abstract
OBJECTIVE: MicroRNAs (miRNAs) are essential biomarkers during development of human diseases. We aimed to explore the role of hypoxia-induced bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-98-5p in myocardial ischemia-reperfusion injury (MI/RI). METHODS: BMSCs were isolated, cultured, stimulated by hypoxia and transfected with adenovirus expressing miR-98-5p. The exosomes were extracted from BMSCs and named as BMSC-exos. The rat MI/RI models were established by ligation of left anterior descending artery and were respectively injected. Then, hemodynamic indices, myocardial enzymes, oxidative stress factors, inflammatory factors, macrophage infiltration and infarct size in these rats were determined. Expression of miR-98-5p, toll-like receptor 4 (TLR4) and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway-related proteins was assessed. The target relation between miR-98-5p and TLR4 was confirmed by bioinformatic method and dual luciferase report gene assay. RESULTS: MiR-98-5p was downregulated, TLR4 was upregulated and the PI3K/Akt signaling pathway was inactivated in MI/RI rat myocardial tissues. Exosomal miR-98-5p from hypoxic BMSCs promoted cardiac function and suppressed myocardial enzyme levels, oxidative stress, inflammation response, macrophage infiltration and infarct size in I/R myocardial tissues. Moreover, TRL4 was targeted by miR-98-5p and miR-98-5p activated PI3K/Akt signaling pathway. CONCLUSION: Hypoxia-induced BMSC-exos elevated miR-98-5p to protect against MI/RI. This study may be helpful for treatment of MI/RI.
OBJECTIVE: MicroRNAs (miRNAs) are essential biomarkers during development of human diseases. We aimed to explore the role of hypoxia-induced bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-98-5p in myocardial ischemia-reperfusion injury (MI/RI). METHODS: BMSCs were isolated, cultured, stimulated by hypoxia and transfected with adenovirus expressing miR-98-5p. The exosomes were extracted from BMSCs and named as BMSC-exos. The rat MI/RI models were established by ligation of left anterior descending artery and were respectively injected. Then, hemodynamic indices, myocardial enzymes, oxidative stress factors, inflammatory factors, macrophage infiltration and infarct size in these rats were determined. Expression of miR-98-5p, toll-like receptor 4 (TLR4) and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway-related proteins was assessed. The target relation between miR-98-5p and TLR4 was confirmed by bioinformatic method and dual luciferase report gene assay. RESULTS: MiR-98-5p was downregulated, TLR4 was upregulated and the PI3K/Akt signaling pathway was inactivated in MI/RI rat myocardial tissues. Exosomal miR-98-5p from hypoxic BMSCs promoted cardiac function and suppressed myocardial enzyme levels, oxidative stress, inflammation response, macrophage infiltration and infarct size in I/R myocardial tissues. Moreover, TRL4 was targeted by miR-98-5p and miR-98-5p activated PI3K/Akt signaling pathway. CONCLUSION: Hypoxia-induced BMSC-exos elevated miR-98-5p to protect against MI/RI. This study may be helpful for treatment of MI/RI.