Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

Abstract The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and ac...

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Autores principales:	Pedro Rodríguez-Jiménez, Lola Fernández-Messina, María C. Ovejero-Benito, Pablo Chicharro, Paula Vera-Tomé, Alicia Vara, Danay Cibrian, Pedro Martínez-Fleta, María Jiménez-Fernández, Inés Sánchez-García, Mar Llamas-Velasco, Francisco Abad-Santos, Francisco Sánchez-Madrid, Esteban Dauden, Hortensia de la Fuente
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29198615589e4c7bba2b3db9df1d1000
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spelling	oai:doaj.org-article:29198615589e4c7bba2b3db9df1d10002021-12-02T16:08:07ZGrowth arrest and DNA damage-inducible proteins (GADD45) in psoriasis10.1038/s41598-021-93780-x2045-2322https://doaj.org/article/29198615589e4c7bba2b3db9df1d10002021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93780-xhttps://doaj.org/toc/2045-2322Abstract The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.Pedro Rodríguez-JiménezLola Fernández-MessinaMaría C. Ovejero-BenitoPablo ChicharroPaula Vera-ToméAlicia VaraDanay CibrianPedro Martínez-FletaMaría Jiménez-FernándezInés Sánchez-GarcíaMar Llamas-VelascoFrancisco Abad-SantosFrancisco Sánchez-MadridEsteban DaudenHortensia de la FuenteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pedro Rodríguez-Jiménez Lola Fernández-Messina María C. Ovejero-Benito Pablo Chicharro Paula Vera-Tomé Alicia Vara Danay Cibrian Pedro Martínez-Fleta María Jiménez-Fernández Inés Sánchez-García Mar Llamas-Velasco Francisco Abad-Santos Francisco Sánchez-Madrid Esteban Dauden Hortensia de la Fuente Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
description	Abstract The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.
format	article
author	Pedro Rodríguez-Jiménez Lola Fernández-Messina María C. Ovejero-Benito Pablo Chicharro Paula Vera-Tomé Alicia Vara Danay Cibrian Pedro Martínez-Fleta María Jiménez-Fernández Inés Sánchez-García Mar Llamas-Velasco Francisco Abad-Santos Francisco Sánchez-Madrid Esteban Dauden Hortensia de la Fuente
author_facet	Pedro Rodríguez-Jiménez Lola Fernández-Messina María C. Ovejero-Benito Pablo Chicharro Paula Vera-Tomé Alicia Vara Danay Cibrian Pedro Martínez-Fleta María Jiménez-Fernández Inés Sánchez-García Mar Llamas-Velasco Francisco Abad-Santos Francisco Sánchez-Madrid Esteban Dauden Hortensia de la Fuente
author_sort	Pedro Rodríguez-Jiménez
title	Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_short	Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_full	Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_fullStr	Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_full_unstemmed	Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_sort	growth arrest and dna damage-inducible proteins (gadd45) in psoriasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29198615589e4c7bba2b3db9df1d1000
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Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

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