Myocardial NF-κB activation is essential for zebrafish heart regeneration.
Published
Journal Article
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-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.
Full Text
Duke Authors
Cited Authors
- Karra, R; Knecht, AK; Kikuchi, K; Poss, KD
Published Date
- October 27, 2015
Published In
Volume / Issue
- 112 / 43
Start / End Page
- 13255 - 13260
PubMed ID
- 26472034
Pubmed Central ID
- 26472034
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.1511209112
Language
- eng
Conference Location
- United States