Cargando…

A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist

Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each moda...

Descripción completa

Detalles Bibliográficos
Autores principales: Papaccio, Federica, Bellei, Barbara, Ottaviani, Monica, D’Arino, Andrea, Truglio, Mauro, Caputo, Silvia, Cigliana, Giovanni, Sciuto, Lorenzo, Migliano, Emilia, Pacifico, Alessia, Iacovelli, Paolo, Picardo, Mauro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688513/
https://www.ncbi.nlm.nih.gov/pubmed/36429011
http://dx.doi.org/10.3390/cells11223583
_version_ 1784836287379800064
author Papaccio, Federica
Bellei, Barbara
Ottaviani, Monica
D’Arino, Andrea
Truglio, Mauro
Caputo, Silvia
Cigliana, Giovanni
Sciuto, Lorenzo
Migliano, Emilia
Pacifico, Alessia
Iacovelli, Paolo
Picardo, Mauro
author_facet Papaccio, Federica
Bellei, Barbara
Ottaviani, Monica
D’Arino, Andrea
Truglio, Mauro
Caputo, Silvia
Cigliana, Giovanni
Sciuto, Lorenzo
Migliano, Emilia
Pacifico, Alessia
Iacovelli, Paolo
Picardo, Mauro
author_sort Papaccio, Federica
collection PubMed
description Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies.
format Online
Article
Text
id pubmed-9688513
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96885132022-11-25 A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist Papaccio, Federica Bellei, Barbara Ottaviani, Monica D’Arino, Andrea Truglio, Mauro Caputo, Silvia Cigliana, Giovanni Sciuto, Lorenzo Migliano, Emilia Pacifico, Alessia Iacovelli, Paolo Picardo, Mauro Cells Article Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies. MDPI 2022-11-12 /pmc/articles/PMC9688513/ /pubmed/36429011 http://dx.doi.org/10.3390/cells11223583 Text en © 2022 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
Papaccio, Federica
Bellei, Barbara
Ottaviani, Monica
D’Arino, Andrea
Truglio, Mauro
Caputo, Silvia
Cigliana, Giovanni
Sciuto, Lorenzo
Migliano, Emilia
Pacifico, Alessia
Iacovelli, Paolo
Picardo, Mauro
A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
title A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
title_full A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
title_fullStr A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
title_full_unstemmed A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
title_short A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
title_sort possible modulator of vitiligo metabolic impairment: rethinking a pparγ agonist
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688513/
https://www.ncbi.nlm.nih.gov/pubmed/36429011
http://dx.doi.org/10.3390/cells11223583
work_keys_str_mv AT papacciofederica apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT belleibarbara apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT ottavianimonica apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT darinoandrea apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT trugliomauro apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT caputosilvia apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT ciglianagiovanni apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT sciutolorenzo apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT miglianoemilia apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT pacificoalessia apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT iacovellipaolo apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT picardomauro apossiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT papacciofederica possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT belleibarbara possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT ottavianimonica possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT darinoandrea possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT trugliomauro possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT caputosilvia possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT ciglianagiovanni possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT sciutolorenzo possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT miglianoemilia possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT pacificoalessia possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT iacovellipaolo possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist
AT picardomauro possiblemodulatorofvitiligometabolicimpairmentrethinkingappargagonist