|ZFIN ID: ZDB-PUB-151019-15|
Myocardial NF-κB activation is essential for zebrafish heart regeneration
Karra, R., Knecht, A.K., Kikuchi, K., Poss, K.D.
|Source:||Proceedings of the National Academy of Sciences of the United States of America 112(43): 13255-60 (Journal)|
|Registered Authors:||Karra, Ravi, Kikuchi, Kazu, Knecht, Anne, Poss, Kenneth D.|
|Keywords:||NF-κB, cardiomyocyte, epicardium, heart regeneration, zebrafish|
|PubMed:||26472034 Full text @ Proc. Natl. Acad. Sci. USA|
Karra, R., Knecht, A.K., Kikuchi, K., Poss, K.D. (2015) Myocardial NF-κB activation is essential for zebrafish heart regeneration. Proceedings of the National Academy of Sciences of the United States of America. 112(43):13255-60.
ABSTRACTHeart 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-κB signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-κB activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation of gata4 regulatory sequences is also prevented by NF-κB signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-κB signaling as a key node between cardiac injury and tissue regeneration.