文章基本信息

标题：Myocardial NF-κB activation is essential for zebrafish heart regeneration
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作者：Ravi Karra ; Anne K. Knecht ; Kazu Kikuchi 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：43
页码：13255-13260
DOI：10.1073/pnas.1511209112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceHeart failure occurs when the heart cannot pump enough blood to meet the body's demands. The heart most often weakens through the loss of muscle cells, called cardiomyocytes. Heart failure is a devastating disease, and one possible cure is to replace the lost cardiomyocytes through regeneration. Unlike humans, zebrafish can efficiently regenerate their hearts after injury. Interestingly, zebrafish heart cells are similar to human heart cells at the molecular level. Understanding how zebrafish can regenerate cardiac tissue can help identify regenerative therapies for humans. Here, we find that NF-{kappa}B signaling is a link between the injury response and the regenerative program in zebrafish. Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferation and reactivation of a cardiac developmental program, as evidenced by induction of gata4 regulatory sequences in regenerating cardiomyocytes. Although many of the cellular determinants of heart regeneration have been elucidated, how injury triggers a regenerative program through dedifferentiation and epicardial activation is a critical outstanding question. Here, we show that NF-{kappa}B signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-{kappa}B activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation of gata4 regulatory sequences is also prevented by NF-{kappa}B signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-{kappa}B signaling as a key node between cardiac injury and tissue regeneration.
关键词：heart regeneration ; cardiomyocyte ; zebrafish ; NF-κB ; epicardium