Tp53 Suppression Promotes Cardiomyocyte Proliferation during Zebrafish Heart Regeneration.

Animals Cell Proliferation / physiology Genes, p53 Myocardium / cytology Myocytes, Cardiac / cytology Regeneration / physiology Tumor Suppressor Protein p53 / genetics Zebrafish Zebrafish Proteins / genetics
Mdm2 Tp53 cardiomyocyte heart regeneration mitogen zebrafish

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
01 09 2020
Historique:
received: 20 04 2020
revised: 06 07 2020
accepted: 07 08 2020
entrez: 3 9 2020
pubmed: 3 9 2020
medline: 29 5 2021
Statut: ppublish

Résumé

Zebrafish regenerate heart muscle through division of pre-existing cardiomyocytes. To discover underlying regulation, we assess transcriptome datasets for dynamic gene networks during heart regeneration and identify suppression of genes associated with the transcription factor Tp53. Cardiac damage leads to fluctuation of Tp53 protein levels, concomitant with induced expression of its central negative regulator, mdm2, in regenerating cardiomyocytes. Zebrafish lacking functional Tp53 display increased indicators of cardiomyocyte proliferation during regeneration, whereas transgenic Mdm2 blockade inhibits injury-induced cardiomyocyte proliferation. Induced myocardial overexpression of the mitogenic factors Nrg1 or Vegfaa in the absence of injury also upregulates mdm2 and suppresses Tp53 levels, and tp53 mutations augment the mitogenic effects of Nrg1. mdm2 induction is spatiotemporally associated with markers of de-differentiation in injury and growth contexts, suggesting a broad role in cardiogenesis. Our findings reveal myocardial Tp53 suppression by mitogen-induced Mdm2 as a regulatory component of innate cardiac regeneration.

Identifiants

DOI: 10.1016/j.celrep.2020.108089 PMID: 32877671 PMC: PMC7494019
pubmed: 32877671
pii: S2211-1247(20)31078-0
doi: 10.1016/j.celrep.2020.108089
pmc: PMC7494019
mid: NIHMS1627845
pii:
doi:

Substances chimiques

Tumor Suppressor Protein p53 0
Zebrafish Proteins 0
tp53 protein, zebrafish 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108089

Subventions

Organisme : NHLBI NIH HHS
ID : R35 HL150713
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Adam Shoffner (A)

Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.

Valentina Cigliola (V)

Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.

Nutishia Lee (N)

Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.

Jianhong Ou (J)

Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.

Kenneth D Poss (KD)

Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: kenneth.poss@duke.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes suppresseurs de tumeur › Gènes p53 › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Myocarde › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › Tp53 Suppression Promotes Cardiomyocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de poisson › Protéines de poisson-zèbre › Tp53 Suppression Promotes Cardiomyocyte...