PUBLICATION
Myocardial NF-κB activation is essential for zebrafish heart regeneration
- Authors
- Karra, R., Knecht, A.K., Kikuchi, K., Poss, K.D.
- ID
- ZDB-PUB-151019-15
- Date
- 2015
- 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
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Chromatin Immunoprecipitation
- DNA Primers/genetics
- Fluorescent Antibody Technique
- Heart/physiology*
- Histological Techniques
- Image Processing, Computer-Assisted
- In Situ Hybridization
- Microscopy, Confocal
- Myocardium/metabolism*
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/physiology*
- NF-kappa B/metabolism*
- Polymerase Chain Reaction
- Regeneration/physiology*
- Zebrafish/physiology*
- PubMed
- 26472034 Full text @ Proc. Natl. Acad. Sci. USA
Citation
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping