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Myocardial NF-κB activation is essential for zebrafish heart regeneration.

Publication ,  Journal Article
Karra, R; Knecht, AK; Kikuchi, K; Poss, KD
Published in: Proc Natl Acad Sci U S A
October 27, 2015

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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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

October 27, 2015

Volume

112

Issue

43

Start / End Page

13255 / 13260

Location

United States

Related Subject Headings

  • Zebrafish
  • Regeneration
  • Polymerase Chain Reaction
  • NF-kappa B
  • Myocytes, Cardiac
  • Myocardium
  • Microscopy, Confocal
  • In Situ Hybridization
  • Image Processing, Computer-Assisted
  • Histological Techniques
 

Citation

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Karra, R., Knecht, A. K., Kikuchi, K., & Poss, K. D. (2015). Myocardial NF-κB activation is essential for zebrafish heart regeneration. Proc Natl Acad Sci U S A, 112(43), 13255–13260. https://doi.org/10.1073/pnas.1511209112
Karra, Ravi, Anne K. Knecht, Kazu Kikuchi, and Kenneth D. Poss. “Myocardial NF-κB activation is essential for zebrafish heart regeneration.Proc Natl Acad Sci U S A 112, no. 43 (October 27, 2015): 13255–60. https://doi.org/10.1073/pnas.1511209112.
Karra R, Knecht AK, Kikuchi K, Poss KD. Myocardial NF-κB activation is essential for zebrafish heart regeneration. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13255–60.
Karra, Ravi, et al. “Myocardial NF-κB activation is essential for zebrafish heart regeneration.Proc Natl Acad Sci U S A, vol. 112, no. 43, Oct. 2015, pp. 13255–60. Pubmed, doi:10.1073/pnas.1511209112.
Karra R, Knecht AK, Kikuchi K, Poss KD. Myocardial NF-κB activation is essential for zebrafish heart regeneration. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13255–13260.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

October 27, 2015

Volume

112

Issue

43

Start / End Page

13255 / 13260

Location

United States

Related Subject Headings

  • Zebrafish
  • Regeneration
  • Polymerase Chain Reaction
  • NF-kappa B
  • Myocytes, Cardiac
  • Myocardium
  • Microscopy, Confocal
  • In Situ Hybridization
  • Image Processing, Computer-Assisted
  • Histological Techniques