Department of Cell Biology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13416-21. doi: 10.1073/pnas.1309810110. Epub 2013 Jul 30.
Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes during heart regeneration. We identified dynamic induction of several Jak1/Stat3 pathway members following trauma, events accompanied by cytokine production. Transgenic Stat3 inhibition in cardiomyocytes restricted injury-induced proliferation and regeneration, but did not reduce cardiogenesis during animal growth. The secreted protein Rln3a was induced in a Stat3-dependent manner by injury, and exogenous Rln3 delivery during Stat3 inhibition stimulated cardiomyocyte proliferation. Our results identify an injury-specific cardiomyocyte program essential for heart regeneration.
某些低等脊椎动物，如斑马鱼，在心脏损伤后会激活储备心肌细胞的增殖，以再生失去的心肌。在这里，我们使用核糖体亲和纯化技术来分析斑马鱼心肌细胞在心脏再生过程中的翻译 RNA。我们发现，创伤后 Jak1/Stat3 通路的几个成员被动态诱导，伴随着细胞因子的产生。在心肌细胞中转基因 Stat3 抑制限制了损伤诱导的增殖和再生，但在动物生长过程中并没有减少心脏发生。分泌蛋白 Rln3a 被损伤以 Stat3 依赖的方式诱导，并且在 Stat3 抑制期间外源性 Rln3 传递刺激心肌细胞增殖。我们的结果确定了一个损伤特异性的心肌细胞程序，对心脏再生至关重要。
