一种能精细调节基因表达的RNA分子可刺激小鼠心脏长出新细胞。该发现开启了用模拟这一可令基因沉默的分子(一种微RNA，或小RNA)的药物来再生心肌并治疗心脏病的可能性。与其它器官不同，成年人的心脏缺乏形成新细胞并修复受伤后损坏的能力。在最近的发现之前，哺乳动物心脏似乎不能再生;这些发现显示，小鼠可在出生后最多达6天的时间内再生心肌细胞(即心脏的肌肉细胞)。Ying Tian和同事想知道他们是否能在成年小鼠中用miR302-367(这是一组微RNA)恢复这一再生潜力，miR302-367在哺乳动物(包括人)的胚胎发育中能驱动细胞增生。他们发现在新生小鼠中，过度表达这种微RNA可促进心肌细胞增生，而删除它则会减弱心肌细胞生长。RNA测序揭示，miR302-367可阻断Hippo信号通路中的基因;该通路的作用是作为一种阻止细胞分裂的分子闸。通过“解除”这一分子闸，miR302-367可诱导心肌细胞重新进入细胞周期并增殖。在心肌梗塞的成年小鼠中激活微RNA可刺激小片的新细胞生长，减少疤痕并修复受损的心肌组织。然而，过长时间表达该微RNA会引起细胞增殖危险性增高，导致心脏增大并最终出现心衰。用一种miR302-367模拟物做短期治疗能让小鼠受伤组织愈合，并同时免除这些副作用。
原文链接：A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice
In contrast to lower vertebrates, the mammalian heart has limited capacity to regenerate after injury in part due to ineffective reactivation of cardiomyocyte proliferation. We show that the microRNA cluster miR302-367 is important for cardiomyocyte proliferation during development and is sufficient to induce cardiomyocyte proliferation in the adult and promote cardiac regeneration. In mice, loss of miR302-367 led to decreased cardiomyocyte proliferation during development. In contrast, increased miR302-367 expression led to a profound increase in cardiomyocyte proliferation, in part through repression of the Hippo signal transduction pathway. Postnatal reexpression of miR302-367 reactivated the cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction. However, long-term expression of miR302-367 induced cardiomyocyte dedifferentiation and dysfunction, suggesting that persistent reactivation of the cell cycle in postnatal cardiomyocytes is not desirable. This limitation can be overcome by transient systemic application of miR302-367 mimics, leading to increased cardiomyocyte proliferation and mass, decreased fibrosis, and improved function after injury. Our data demonstrate the ability of microRNA-based therapeutic approaches to promote mammalian cardiac repair and regeneration through the transient activation of cardiomyocyte proliferation.
