Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7

被引：128
作者：
Chen, Qi [1 ]
Liu, Yu [2 ]
Ding, Xueyan [3 ]
Li, Qinfeng [1 ]
Qiu, Fuyu [1 ]
Wang, Meihui [1 ]
Shen, Zhida [1 ]
Zheng, Hao [3 ]
Fu, Guosheng [1 ]
机构：
[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Biomed Res Ctr, Dept Cardiol,Sch Med, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China
[2] Nanjing Univ, Sch Med, Affiliated Nanjing Drum Tower Hosp, Dept Cardiol, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China
[3] Zhejiang Prov Peoples Hosp, Dept Cardiol, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China
来源：
MOLECULAR AND CELLULAR BIOCHEMISTRY | 2020年 / 465卷 / 1-2期
关键词：
Ischemia reperfusion; Exosomes; miR-125b; Apoptosis; Inflammatory factor; ISCHEMIA/REPERFUSION INJURY; APOPTOSIS; STRESS; SUPPRESSES; MECHANISM; GROWTH;
D O I：
10.1007/s11010-019-03671-z
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
MicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosomes carrying miR-125b on I/R rats. The myocardial I/R model in rats was constructed by ligation of the left anterior descending coronary artery (LAD). Rats were randomly divided into I/R and Sham group. Lv-cel-miR-67 (control) or Lv-miR-125b was transfected into BMSCs. Exosomes were extracted from transfected BMSCs, and separately named BMSC-Exo-67, BMSC-Exo-125b, and BMSC-Exo. MTT assay and flow cytometry were used to detect the viability and apoptosis of I/R myocardium cells, respectively. The expression of cell apoptosis proteins and the levels of inflammatory factors were examined by Western blot and ELISA assay, respectively. The target relationship between miR-125b and SIRT7 was predicted by using StarBase3.0, and was confirmed by using dual-luciferase reporter gene assay. qRT-PCR, immunohistochemistry staining, and Western blot were used to evaluate the expression of SIRT7 in myocardium tissues in I/R rats. BMSC-derived exosomes were successfully isolated and identified by TEM and positive expression of CD9 and CD63. The expression of miR-125b was down-regulated in I/R myocardium tissues and cells. BMSC-Exo-125b significantly up-regulated miR-125b in I/R myocardium cells. The intervention of BMSC-Exo-125b significantly increased the cell viability, decreased the apoptotic ratio, down-regulated Bax and caspase-3, up-regulated Bcl-2, and decreased the levels of IL-1 beta, IL-6, and TNF-alpha in I/R myocardium cells. SIRT7 was a target of miR-125b, and BMSC-Exo-125b significantly down-regulated SIRT7 in myocardium cells. In addition, the injection of BMSC-Exo-125b alleviated the pathological damages and down-regulated SIRT7 in myocardium tissues of I/R rats. BMSC-derived exosomes carrying miR-125b protected against myocardial I/R by targeting SIRT7.
引用
收藏
页码：103 / 114
页数：12
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