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NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted thera...

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Autores principales: Arroyo, Ana B., Bernal-Carrión, Martín, Cantón-Sandoval, Joaquín, Cabas, Isabel, Corbalán-Vélez, Raúl, Martínez-Menchón, Teresa, Ferri, Belén, Cayuela, María L., García-Moreno, Diana, Mulero, Victoriano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178103/
https://www.ncbi.nlm.nih.gov/pubmed/37175698
http://dx.doi.org/10.3390/ijms24097992
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author Arroyo, Ana B.
Bernal-Carrión, Martín
Cantón-Sandoval, Joaquín
Cabas, Isabel
Corbalán-Vélez, Raúl
Martínez-Menchón, Teresa
Ferri, Belén
Cayuela, María L.
García-Moreno, Diana
Mulero, Victoriano
author_facet Arroyo, Ana B.
Bernal-Carrión, Martín
Cantón-Sandoval, Joaquín
Cabas, Isabel
Corbalán-Vélez, Raúl
Martínez-Menchón, Teresa
Ferri, Belén
Cayuela, María L.
García-Moreno, Diana
Mulero, Victoriano
author_sort Arroyo, Ana B.
collection PubMed
description Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD(+) and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD(+), mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD(+) and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.
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spelling pubmed-101781032023-05-13 NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis Arroyo, Ana B. Bernal-Carrión, Martín Cantón-Sandoval, Joaquín Cabas, Isabel Corbalán-Vélez, Raúl Martínez-Menchón, Teresa Ferri, Belén Cayuela, María L. García-Moreno, Diana Mulero, Victoriano Int J Mol Sci Article Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD(+) and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD(+), mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD(+) and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients. MDPI 2023-04-28 /pmc/articles/PMC10178103/ /pubmed/37175698 http://dx.doi.org/10.3390/ijms24097992 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arroyo, Ana B.
Bernal-Carrión, Martín
Cantón-Sandoval, Joaquín
Cabas, Isabel
Corbalán-Vélez, Raúl
Martínez-Menchón, Teresa
Ferri, Belén
Cayuela, María L.
García-Moreno, Diana
Mulero, Victoriano
NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
title NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
title_full NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
title_fullStr NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
title_full_unstemmed NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
title_short NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
title_sort nampt and parylation are involved in the pathogenesis of atopic dermatitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178103/
https://www.ncbi.nlm.nih.gov/pubmed/37175698
http://dx.doi.org/10.3390/ijms24097992
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