GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.

The growth arrest and DNA damage inducible 45A (GADD45A) is a multifaceted protein associated with stress signaling and cellular injury. Aside its well-established tumor suppressor activity, recent studies point to additional roles for GADD45A, including the regulation of catabolic and anabolic path...

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Autores: Rostami A, Palomer X, Pizarro-Delgado J, Peña L, Zamora M, Montori-Grau M, Barroso E, Valenzuela-Alcaraz B, Crispi F, Salvador JM, García R, Hurlé MA, Nistal F, Vázquez-Carrera M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p28557
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28557
Access Level:acceso abierto
Palabra clave:Apoptosis
Cardiac hypertrophy
GADD45A
Inflammation and fibrosis
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spelling GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.Rostami APalomer XPizarro-Delgado JPeña LZamora MMontori-Grau MBarroso EValenzuela-Alcaraz BCrispi FSalvador JMGarcía RHurlé MANistal FVázquez-Carrera MApoptosisCardiac hypertrophyGADD45AInflammation and fibrosisThe growth arrest and DNA damage inducible 45A (GADD45A) is a multifaceted protein associated with stress signaling and cellular injury. Aside its well-established tumor suppressor activity, recent studies point to additional roles for GADD45A, including the regulation of catabolic and anabolic pathways, or the prevention of inflammation, fibrosis, and oxidative stress in some tissues and organs. However, little is known about its function in cardiac disease. In this study, we aimed to evaluate the role of GADD45A in the heart by using mice with constitutive and systemic deletion of Gadd45a, and cardiac cells of human origin. Gadd45a suppression in knockout mice triggered cardiac fibrosis, inflammation, and apoptosis, and these changes correlated with an hyperactivation of the pro-inflammatory and pro-fibrotic transcription factors activator protein-1 (AP-1), nuclear factor-?B (NF-?B), and signal transducer and activator of transcription 3 (STAT3). Deletion of Gadd45a also resulted in substantial cardiac hypertrophy, which negatively impacted cardiac morphology and function in knockout mice. Consistent with this, GADD45A overexpression in human AC16 cardiomyocytes partially prevented the inflammatory and fibrotic responses induced by tumor necrosis factor-a (TNF-a). Overall, data presented in this study highlight an important role for GADD45A in the heart, since it may prevent inflammation, fibrosis, and apoptosis, and, by this means, preserve cardiac function and performance. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy and subsequent heart failure, these results suggest that promoting the activity of this protein might be a promising therapeutic strategy to slow down the progression of these deleterious diseases.SPRINGER BASEL AG2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28557CELLULAR AND MOLECULAR LIFE SCIENCESISSN: 1420682XISSNe: 14209071reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p285572026-05-27T12:37:41Z
dc.title.none.fl_str_mv GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
title GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
spellingShingle GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
Rostami A
Apoptosis
Cardiac hypertrophy
GADD45A
Inflammation and fibrosis
title_short GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
title_full GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
title_fullStr GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
title_full_unstemmed GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
title_sort GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.
dc.creator.none.fl_str_mv Rostami A
Palomer X
Pizarro-Delgado J
Peña L
Zamora M
Montori-Grau M
Barroso E
Valenzuela-Alcaraz B
Crispi F
Salvador JM
García R
Hurlé MA
Nistal F
Vázquez-Carrera M
author Rostami A
author_facet Rostami A
Palomer X
Pizarro-Delgado J
Peña L
Zamora M
Montori-Grau M
Barroso E
Valenzuela-Alcaraz B
Crispi F
Salvador JM
García R
Hurlé MA
Nistal F
Vázquez-Carrera M
author_role author
author2 Palomer X
Pizarro-Delgado J
Peña L
Zamora M
Montori-Grau M
Barroso E
Valenzuela-Alcaraz B
Crispi F
Salvador JM
García R
Hurlé MA
Nistal F
Vázquez-Carrera M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Cardiac hypertrophy
GADD45A
Inflammation and fibrosis
topic Apoptosis
Cardiac hypertrophy
GADD45A
Inflammation and fibrosis
description The growth arrest and DNA damage inducible 45A (GADD45A) is a multifaceted protein associated with stress signaling and cellular injury. Aside its well-established tumor suppressor activity, recent studies point to additional roles for GADD45A, including the regulation of catabolic and anabolic pathways, or the prevention of inflammation, fibrosis, and oxidative stress in some tissues and organs. However, little is known about its function in cardiac disease. In this study, we aimed to evaluate the role of GADD45A in the heart by using mice with constitutive and systemic deletion of Gadd45a, and cardiac cells of human origin. Gadd45a suppression in knockout mice triggered cardiac fibrosis, inflammation, and apoptosis, and these changes correlated with an hyperactivation of the pro-inflammatory and pro-fibrotic transcription factors activator protein-1 (AP-1), nuclear factor-?B (NF-?B), and signal transducer and activator of transcription 3 (STAT3). Deletion of Gadd45a also resulted in substantial cardiac hypertrophy, which negatively impacted cardiac morphology and function in knockout mice. Consistent with this, GADD45A overexpression in human AC16 cardiomyocytes partially prevented the inflammatory and fibrotic responses induced by tumor necrosis factor-a (TNF-a). Overall, data presented in this study highlight an important role for GADD45A in the heart, since it may prevent inflammation, fibrosis, and apoptosis, and, by this means, preserve cardiac function and performance. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy and subsequent heart failure, these results suggest that promoting the activity of this protein might be a promising therapeutic strategy to slow down the progression of these deleterious diseases.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28557
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28557
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGER BASEL AG
publisher.none.fl_str_mv SPRINGER BASEL AG
dc.source.none.fl_str_mv CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN: 1420682X
ISSNe: 14209071
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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