Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration
Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration
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DOI：
10.1073/pnas.1309810110
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发表时间：
2013-08-13
影响因子：
11.1
通讯作者：
Poss, Kenneth D.
中科院分区：
文献类型：
--
作者：
Fang, Yi;Gupta, Vikas;Poss, Kenneth D.
某些低等脊椎动物，如斑马鱼，在心脏损伤后激活备用心肌细胞的增殖，以再生失去的心肌。在这里，我们使用翻译核糖体亲和纯化来分析心脏再生过程中斑马鱼心肌细胞中的翻译RNA。我们确定了几个Jak 1/Stat 3途径成员的动态诱导创伤后，事件伴随着细胞因子的产生。心肌细胞中的转基因Stat 3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。通过损伤以Stat 3依赖性方式诱导分泌蛋白Rln 3a，并且在Stat 3抑制期间递送外源性Rln 3刺激心肌细胞增殖。我们的研究结果确定了心脏再生所必需的损伤特异性心肌细胞程序。
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.