The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.
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 ma...
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doaj-de20ba6fa07744ed9e23e6a591b490e22020-11-25T02:35:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7329410.1371/journal.pone.0073294The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.Renata WindakJulius MüllerAllison FelleyAlexander AkhmedovErwin F WagnerThierry PedrazziniGrzegorz SumaraRomeo RicciSystemic 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.http://europepmc.org/articles/PMC3769267?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Renata Windak Julius Müller Allison Felley Alexander Akhmedov Erwin F Wagner Thierry Pedrazzini Grzegorz Sumara Romeo Ricci |
spellingShingle |
Renata Windak Julius Müller Allison Felley Alexander Akhmedov Erwin F Wagner Thierry Pedrazzini Grzegorz Sumara Romeo Ricci The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. PLoS ONE |
author_facet |
Renata Windak Julius Müller Allison Felley Alexander Akhmedov Erwin F Wagner Thierry Pedrazzini Grzegorz Sumara Romeo Ricci |
author_sort |
Renata Windak |
title |
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. |
title_short |
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. |
title_full |
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. |
title_fullStr |
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. |
title_full_unstemmed |
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. |
title_sort |
ap-1 transcription factor c-jun prevents stress-imposed maladaptive remodeling of the heart. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3769267?pdf=render |
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