nature20121220-2

来自意大利国际基因工程与生物技术中心的一个研究小组通过导入两个微RNA到受损的小鼠心脏中而成功地导致心脏组织再生。研究人员是在进行大量的研究之后才发现这两个不可缺少的miR的。

-2012年12月20日《自然》


中文翻译


【题目】功能性筛选鉴定出诱导心脏再生的miRNA

【译文】哺乳动物中,胚胎发育期间心脏扩大主要依赖心肌细胞数量的增加。然而,出生后心肌细胞停止增殖,而且心肌层的进一步生长是通过现存肌细胞的肥大扩展产生的。成年期,作为心肌细胞最小限度再生的结果,通过心肌再生的心脏损伤修复是非常有限的。本研究表明外源性给予筛选的microRNAs (miRNAs)会显著刺激心肌细胞增殖,并促进心脏修复。 利用全基因组miRNA文库,我们对可促进新生心肌细胞增殖的人miRNAs展开了高容量显微镜检查法以及高通量的功能筛选。40个miRNA可以强烈的增加新生小鼠和大鼠心肌细胞的DNA合成和细胞质分裂。其中两个miRNA(hsa-miR-590 和hsa-miR-199a)被进一步选择用以测试,并表明这两个miRNA在体外可以促进成熟心肌细胞的细胞周期再进入,并在新生和成熟动物中促进心肌细胞的增殖。小鼠发生心肌梗死后,这些miRNA可以刺激明显的心脏再生,并几乎可以完全恢复心脏功能。已鉴定的miRNA为心肌细胞损失引起的心脏疾病的治疗带来了希望。

英文原稿


[Title]: Functional screening identifies miRNAs inducing cardiac regeneration

[Authors]:Ana Eulalio,1, 3 Miguel Mano,1 Matteo Dal Ferro,1, 2 Lorena Zentilin,1 Gianfranco Sinagra,2 Serena Zacchigna1 & Mauro Giacca1

[Abstract]In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.

原文地址

http://www.nature.com/nature/journal/v492/n7429/full/nature11739.html

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