Immunology and Oncology Department, National Center for Biotechnology, CSIC, 28049 Madrid, Spain; Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain; Cardiovascular Area, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15706 Santiago de Compostela, Spain.
Stem Cell Reports. 2014 Dec 9;3(6):1029-42. doi: 10.1016/j.stemcr.2014.10.010. Epub 2014 Nov 20.
miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation. The beneficial effects of miR-133a-CPCs seem to correlate with the upregulated expression of several relevant paracrine factors and the plausible cooperative secretion of miR-133a via exosomal transport. Finally, an in vitro heart muscle model confirmed the antiapoptotic effects of miR-133a-CPCs, favoring the structuration and contractile functionality of the artificial tissue.
miR-133a 和 miR-1 被称为肌肉特异性 microRNAs，参与心脏发育和病理生理学。我们已经表明，miR-1 和 miR-133a 在成年心脏祖细胞（CPCs）的体外心脏分化过程中都是早期且逐渐上调的，但只有 miR-133a 的表达在体外氧化应激下增强。miR-1 有利于 CPCs 的分化，而 miR-133a 的过表达则可以保护 CPCs 免受细胞死亡，其靶标包括促凋亡基因 Bim 和 Bmf。miR-133a-CPCs 通过减少纤维化和肥大、增加血管生成和心肌细胞增殖，明显改善了大鼠心肌梗死模型中的心脏功能。miR-133a-CPCs 的有益作用似乎与几个相关旁分泌因子的上调表达以及通过外泌体运输推测的 miR-133a 的协同分泌相关。最后，体外心肌模型证实了 miR-133a-CPCs 的抗凋亡作用，有利于人工组织的结构和收缩功能。
