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.

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. - In: CELLS. - ISSN 2073-4409. - 11:22(2022). [10.3390/cells11223583]

A possible modulator of vitiligo metabolic impairment: rethinking a PPARγ agonist

Federica Papaccio
;
Andrea D'Arino;Mauro Truglio;Silvia Caputo;Lorenzo Sciuto;Emilia Migliano;
2022

Abstract

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.
2022
pparγ; cellular metabolism; fibroblasts; glucose metabolism; melanocytes; metabolic impairment; pioglitazone; vitiligo
01 Pubblicazione su rivista::01a Articolo in rivista
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. - In: CELLS. - ISSN 2073-4409. - 11:22(2022). [10.3390/cells11223583]
File allegati a questo prodotto
File Dimensione Formato  
Papaccio_Possible-modulator_2024.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.75 MB
Formato Adobe PDF
2.75 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1725827
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 9
social impact