miRNA in cardiac development and regeneration.
miRNA in cardiac development and regeneration.
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心脏发育和再生中的 miRNA。
DOI：
10.1186/s13619-021-00077-5
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发表时间：
2021-06-01
期刊：
影响因子：
--
通讯作者：
Wei K
中科院分区：
文献类型：
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作者：
Ouyang Z;Wei K
缺血性心脏病是世界范围内发病率和死亡率的主要原因之一。在成年哺乳动物心脏中，大多数心肌细胞是终末分化的，增殖能力极其有限，使得心肌梗死等损伤后无法再生心脏。MicroRNAs(MiRNAs)是一类非编码的单链RNA，参与mRNA沉默和转录后基因表达的调节，在心脏发育和心肌细胞增殖中发挥重要作用。肌特异性miRNAs如miR-1是心肌细胞成熟和生长的关键调节因子，而miR-199-3p和其他miRNAs则显示出强大的诱导心肌细胞增殖的活性。由于其体积小和相对多效性，miRNAs作为心脏再生的治疗靶点或工具受到了极大的关注。越来越多的研究表明，特定miRNAs的过度表达或抑制可以诱导心肌细胞增殖和心脏再生。在多个物种中发现了一些促进增殖的miRNAs的共同靶点，如Hippo-Yap信号通路，突显了miRNAs作为探针剖析生物过程的核心调控因子的能力。许多miRNAs已被证明可以改善小鼠心肌梗死后的心功能，一项在猪身上的试验也显示了良好的结果。然而，技术上的困难，特别是在交付方法方面，以及不受控制的扩散等不利影响仍然存在。本文综述了miRNA在心脏发育和再生中的研究进展，探讨了miRNA调控心肌细胞增殖的机制，并探讨了其作为心脏再生治疗新策略的潜力。
Ischemic heart disease is one of the main causes of morbidity and mortality in the world. In adult mammalian hearts, most cardiomyocytes are terminally differentiated and have extremely limited capacity of proliferation, making it impossible to regenerate the heart after injuries such as myocardial infarction. MicroRNAs (miRNAs), a class of non-coding single-stranded RNA, which are involved in mRNA silencing and the regulation of post-transcriptional gene expression, have been shown to play a crucial role in cardiac development and cardiomyocyte proliferation. Muscle specific miRNAs such as miR-1 are key regulators of cardiomyocyte maturation and growth, while miR-199-3p and other miRNAs display potent activity to induce proliferation of cardiomyocytes. Given their small size and relative pleiotropic effects, miRNAs have gained significant attraction as promising therapeutic targets or tools in cardiac regeneration. Increasing number of studies demonstrated that overexpression or inhibition of specific miRNAs could induce cardiomyocyte proliferation and cardiac regeneration. Some common targets of pro-proliferation miRNAs, such as the Hippo-Yap signaling pathway, were identified in multiple species, highlighting the power of miRNAs as probes to dissect core regulators of biological processes. A number of miRNAs have been shown to improve heart function after myocardial infarction in mice, and one trial in swine also demonstrated promising outcomes. However, technical difficulties, especially in delivery methods, and adverse effects, such as uncontrolled proliferation, remain. In this review, we summarize the recent progress in miRNA research in cardiac development and regeneration, examine the mechanisms of miRNA regulating cardiomyocyte proliferation, and discuss its potential as a new strategy for cardiac regeneration therapy.