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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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Autores principales: Windak, Renata, Müller, Julius, Felley, Allison, Akhmedov, Alexander, Wagner, Erwin F., Pedrazzini, Thierry, Sumara, Grzegorz, Ricci, Romeo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769267/
https://www.ncbi.nlm.nih.gov/pubmed/24039904
http://dx.doi.org/10.1371/journal.pone.0073294
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author Windak, Renata
Müller, Julius
Felley, Allison
Akhmedov, Alexander
Wagner, Erwin F.
Pedrazzini, Thierry
Sumara, Grzegorz
Ricci, Romeo
author_facet Windak, Renata
Müller, Julius
Felley, Allison
Akhmedov, Alexander
Wagner, Erwin F.
Pedrazzini, Thierry
Sumara, Grzegorz
Ricci, Romeo
author_sort Windak, Renata
collection PubMed
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.
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spelling pubmed-37692672013-09-13 The AP-1 Transcription Factor c-Jun Prevents Stress-Imposed Maladaptive Remodeling of the Heart Windak, Renata Müller, Julius Felley, Allison Akhmedov, Alexander Wagner, Erwin F. Pedrazzini, Thierry Sumara, Grzegorz Ricci, Romeo PLoS One Research Article 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. Public Library of Science 2013-09-10 /pmc/articles/PMC3769267/ /pubmed/24039904 http://dx.doi.org/10.1371/journal.pone.0073294 Text en © 2013 Windak et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Windak, Renata
Müller, Julius
Felley, Allison
Akhmedov, Alexander
Wagner, Erwin F.
Pedrazzini, Thierry
Sumara, Grzegorz
Ricci, Romeo
The AP-1 Transcription Factor c-Jun Prevents Stress-Imposed Maladaptive Remodeling of the Heart
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769267/
https://www.ncbi.nlm.nih.gov/pubmed/24039904
http://dx.doi.org/10.1371/journal.pone.0073294
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