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
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.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping