miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4.
miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4.
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miR-10a通过KLF4使衰老的人间充质干细胞恢复活力并改善心肌梗塞后的心脏功能
DOI：
10.1186/s13287-018-0895-0
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发表时间：
2018-05-30
影响因子：
7.5
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Dong J;Zhang Z;Huang H;Mo P;Cheng C;Liu J;Huang W;Tian C;Zhang C;Li J
背景衰老是调节人骨髓间充质干细胞（hBM-MSCs）功能及相关microRNA（miRNA）表达变化的关键因素之一。然而，在hBM-MSCs.MethodsWe老化相关的miRNA的变化报道的数据是有限的，以前证明，miR-10a显着减少，在老年hBM-MSCs和恢复的miR-10a水平衰减细胞衰老，并通过抑制Krüpple样因子4（KLF 4）增加老年hBM-MSCs的分化能力。在本研究中，miR-10a过表达或KLF 4在老年hBM-MSCs中通过慢病毒转导下调。体外研究缺氧诱导的老化hBM-MSCs凋亡、细胞存活和细胞旁分泌功能。在体内，将miR-10a过表达或KLF 4下调的老年hBM-MSC植入心肌梗死（MI）后的梗死小鼠心脏中。结果通过慢病毒介导的miR-10a上调和KLF 4下调体外老化hBM-MSCs，我们发现miR-10a通过抑制KLF 4-BAX/BCL 2通路减少缺氧诱导的细胞凋亡，增加老化hBM-MSCs的细胞存活。在体内，移植miR-10a过表达的老化hBM-MSCs促进了植入的干细胞存活并改善了MI后的心功能。结论miR-10a能使衰老hBM-MSCs再生，促进损伤小鼠心脏血管生成，改善心功能。
BackgroundAging is one of the key factors that regulate the function of human bone marrow mesenchymal stem cells (hBM-MSCs) and related changes in microRNA (miRNA) expression. However, data reported on aging-related miRNA changes in hBM-MSCs are limited.MethodsWe demonstrated previously that miR-10a is significantly decreased in aged hBM-MSCs and restoration of the miR-10a level attenuated cell senescence and increased the differentiation capacity of aged hBM-MSCs by repressing Krüpple-like factor 4 (KLF4). In the present study, miR-10a was overexpressed or KLF4 was downregulated in old hBM-MSCs by lentiviral transduction. The hypoxia-induced apoptosis, cell survival, and cell paracrine function of aged hBM-MSCs were investigated in vitro. In vivo, miR-10a-overexpressed or KLF4-downregulated old hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI). The mouse cardiac function of cardiac angiogenesis was measured and cell survival of aged hBM-MSCs was investigated.ResultsThrough lentivirus-mediated upregulation of miR-10a and downregulation of KLF4 in aged hBM-MSCs in vitro, we revealed that miR-10a decreased hypoxia-induced cell apoptosis and increased cell survival of aged hBM-MSCs by repressing the KLF4–BAX/BCL2 pathway. In vivo, transplantation of miR-10a-overexpressed aged hBM-MSCs promoted implanted stem cell survival and improved cardiac function after MI. Mechanistic studies revealed that overexpression of miR-10a in aged hBM-MSCs activated Akt and stimulated the expression of angiogenic factors, thus increasing angiogenesis in ischemic mouse hearts.ConclusionsmiR-10a rejuvenated aged hBM-MSCs which improved angiogenesis and cardiac function in injured mouse hearts.
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影响因子：
5.6
作者：
Li, Jiao;Dong, Jun;Zhang, Zhen-Hui;Zhang, Dong-Cheng;You, Xiang-Yu;Zhong, Yun;Chen, Min-Sheng;Liu, Shi-Ming
通讯作者：
Liu, Shi-Ming
影响因子：
37.3
作者：
Bryant A;Palma CA;Jayaswal V;Yang YW;Lutherborrow M;Ma DD
通讯作者：
Ma DD
影响因子：
4.6
作者：
Xiao GY;Cheng CC;Chiang YS;Cheng WT;Liu IH;Wu SC
通讯作者：
Wu SC
影响因子：
13.5
作者：
Bromage, Daniel I.;Davidson, Sean M.;Yellon, Derek M.
通讯作者：
Yellon, Derek M.
影响因子：
6.1
作者：
Assou, S.;Al-edani, T.;Hamamah, S.
通讯作者：
Hamamah, S.