Karra, Ravi and Knecht, Anne K and Kikuchi, Kazu and Poss, Kenneth 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). pp.13255-60. ISSN 1091-6490 (OA)
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Article available for free from PMC website. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 28 Jan 2016 03:52 |
| Last Modified: | 15 Feb 2017 22:42 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/258 |
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