Targeted MicroRNA Interference Promotes Postnatal Cardiac Cell Cycle Re-Entry.
Targeted MicroRNA Interference Promotes Postnatal Cardiac Cell Cycle Re-Entry.
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DOI：
10.4172/2325-9620.1000108
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Marbán E
中科院分区：
文献类型：
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作者：
Zhang Y;Matsushita N;Eigler T;Marbán E
哺乳动物心脏细胞在出生后不久增殖活性显着降低，此后主要通过肥大生长。我们对心脏成熟和衰老分子机制的理解主要基于全心脏水平的研究。在这里，我们研究了纯化的新生儿和成人心肌细胞获得性静止的分子基础，并使用 microRNA 干扰作为促进心肌细胞细胞周期重新进入的新策略。在心肌细胞出生后成熟过程中，细胞周期蛋白和细胞周期蛋白依赖性激酶（CDK）和正调节剂的表达下调，而CDK抑制剂和负细胞周期调节剂的表达上调。 microRNA 的表达模式也发生了巨大变化，包括 miR-29a、miR-30a 和 miR-141 的增加。用 miRNA 抑制剂抗 miR-29a、抗 miR-30a 和抗 miR-141 处理新生儿心肌细胞，可产生更多的循环细胞并增强细胞周期蛋白 A2 (CCNA2) 的表达。因此，靶向 microRNA 干扰可以重新激活出生后心肌细胞增殖。
Mammalian heart cells undergo a marked reduction in proliferative activity shortly after birth, and thereafter grow predominantly by hypertrophy. Our understanding of the molecular mechanisms underlying cardiac maturation and senescence is based largely on studies at the whole-heart level. Here, we investigate the molecular basis of the acquired quiescence of purified neonatal and adult cardiomyocytes, and use microRNA interference as a novel strategy to promote cardiomyocyte cell cycle re-entry. Expression of cyclins and cyclin-dependent kinases (CDKs) and positive modulators were down-regulated, while CDK inhibitors and negative cell cycle modulators were up-regulated during postnatal maturation of cardiomyocytes. The expression pattern of microRNAs also changed dramatically, including increases in miR-29a, miR-30a and miR-141. Treatment of neonatal cardiomyocytes with miRNA inhibitors anti-miR-29a, anti-miR-30a, and antimiR-141 resulted in more cycling cells and enhanced expression of Cyclin A2 (CCNA2). Thus, targeted microRNA interference can reactivate postnatal cardiomyocyte proliferation.