RT Journal Article
T1 Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
A1 Rodríguez-Jiménez, Pedro
A1 Fernández Messina, Lola María
A1 Ovejero-Benito, María
A1 Chicharro, Pablo
A1 Vera-Tomé, Paula
A1 Vara, Alicia
A1 Cibrian, Danay
A1 Martínez-Fleta, Pedro
A1 Jiménez-Fernández, María
A1 Sánchez-García, Inés
A1 Llamas-Velasco, Mar
A1 Abad-Santos, Francisco
A1 Sánchez-Madrid, Francisco
A1 Dauden, Esteban
A1 Fuente, Hortensia de la
AB 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.
PB Nature Research
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/97235
UL https://hdl.handle.net/20.500.14352/97235
LA eng
NO Rodríguez-Jiménez, P., Fernández-Messina, L., Ovejero-Benito, M.C. et al. Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis. Sci Rep 11, 14579 (2021). https://doi.org/10.1038/s41598-021-93780-x
NO AcknowledgementsInstituto de Salud Carlos III (AES 2017): PI17/01972 to E.D. Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. This research has been co-financed by Fondo Europeo de Desarrollo Regional (FEDER).
NO Fundación BBVA
NO Fundación "la Caixa"
NO Ministerio de Economía y Competitividad (España)
NO European Commission
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 25 abr 2025