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...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/22/3583 |
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| author | Federica Papaccio Barbara Bellei Monica Ottaviani Andrea D’Arino Mauro Truglio Silvia Caputo Giovanni Cigliana Lorenzo Sciuto Emilia Migliano Alessia Pacifico Paolo Iacovelli Mauro Picardo |
| author_facet | Federica Papaccio Barbara Bellei Monica Ottaviani Andrea D’Arino Mauro Truglio Silvia Caputo Giovanni Cigliana Lorenzo Sciuto Emilia Migliano Alessia Pacifico Paolo Iacovelli Mauro Picardo |
| author_sort | Federica Papaccio |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T18:25:13Z |
| format | Article |
| id | doaj.art-33509476e8534960a4a15b8b6c0947be |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T18:25:13Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-33509476e8534960a4a15b8b6c0947be2023-11-24T07:57:45ZengMDPI AGCells2073-44092022-11-011122358310.3390/cells11223583A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ AgonistFederica Papaccio0Barbara Bellei1Monica Ottaviani2Andrea D’Arino3Mauro Truglio4Silvia Caputo5Giovanni Cigliana6Lorenzo Sciuto7Emilia Migliano8Alessia Pacifico9Paolo Iacovelli10Mauro Picardo11Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyClinical Pathology Unit, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyPlastic and Regenerative Surgery, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyPhototherapy Unit, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyPhototherapy Unit, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyCutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyVitiligo 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.https://www.mdpi.com/2073-4409/11/22/3583vitiligoPPARγpioglitazonemelanocytesfibroblastscellular metabolism |
| spellingShingle | Federica Papaccio Barbara Bellei Monica Ottaviani Andrea D’Arino Mauro Truglio Silvia Caputo Giovanni Cigliana Lorenzo Sciuto Emilia Migliano Alessia Pacifico Paolo Iacovelli Mauro Picardo A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist Cells vitiligo PPARγ pioglitazone melanocytes fibroblasts cellular metabolism |
| 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 | vitiligo PPARγ pioglitazone melanocytes fibroblasts cellular metabolism |
| url | https://www.mdpi.com/2073-4409/11/22/3583 |
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