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

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
Druh dokumentu: article
ISSN: 2045-2322
29198615
DOI: 10.1038/s41598-021-93780-x
Popis: 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.
Databáze: Directory of Open Access Journals
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