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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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