The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.

Détails

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_20FC8552CD3B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.
Périodique
Plos One
Auteur⸱e⸱s
Windak R., Müller J., Felley A., Akhmedov A., Wagner E.F., Pedrazzini T., Sumara G., Ricci R.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
8
Numéro
9
Pages
e73294
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Résumé
Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/01/2014 11:32
Dernière modification de la notice
20/08/2019 13:57
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