摘要
Ischemic heart disease is one of the main causes of morbidity and mortality in the world. In adult mammalianhearts, 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), aclass of non-coding single-stranded RNA, which are involved in mRNA silencing and the regulation of posttranscriptionalgene expression, have been shown to play a crucial role in cardiac development and cardiomyocyteproliferation. 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 theirsmall size and relative pleiotropic effects, miRNAs have gained significant attraction as promising therapeutic targetsor tools in cardiac regeneration. Increasing number of studies demonstrated that overexpression or inhibition ofspecific miRNAs could induce cardiomyocyte proliferation and cardiac regeneration. Some common targets of proproliferationmiRNAs, such as the Hippo-Yap signaling pathway, were identified in multiple species, highlighting thepower of miRNAs as probes to dissect core regulators of biological processes. A number of miRNAs have beenshown to improve heart function after myocardial infarction in mice, and one trial in swine also demonstratedpromising outcomes. However, technical difficulties, especially in delivery methods, and adverse effects, such asuncontrolled proliferation, remain. In this review, we summarize the recent progress in miRNA research in cardiacdevelopment and regeneration, examine the mechanisms of miRNA regulating cardiomyocyte proliferation, anddiscuss its potential as a new strategy for cardiac regeneration therapy.
基金
This work was supported by Key Research and Development Program,Ministry of Science and Technology of China(2017YFA0105601,2018YFA0800104)
National Natural Science Foundation of China(31771613,32070823)
Fundamental Research Funds for the Central Universities(22120200411).
