PGC-1s shape epidermal physiology by modulating keratinocyte proliferation and terminal differentiation.

dermatology human metabolism molecular mechanism of gene regulation physiology

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
21 Apr 2023
Historique:
received: 21 07 2022
revised: 02 12 2022
accepted: 26 02 2023
medline: 4 4 2023
entrez: 3 4 2023
pubmed: 4 4 2023
Statut: epublish

Résumé

Skin plays central roles in systemic physiology, and it undergoes significant functional changes during aging. Members of the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1) family (PGC-1s) are key regulators of the biology of numerous tissues, yet we know very little about their impact on skin functions. Global gene expression profiling and gene silencing in keratinocytes uncovered that PGC-1s control the expression of metabolic genes as well as that of terminal differentiation programs. Glutamine emerged as a key substrate promoting mitochondrial respiration, keratinocyte proliferation, and the expression of PGC-1s and terminal differentiation programs. Importantly, gene silencing of PGC-1s reduced the thickness of a reconstructed living human epidermal equivalent. Exposure of keratinocytes to a salicylic acid derivative potentiated the expression of PGC-1s and terminal differentiation genes and increased mitochondrial respiration. Overall, our results show that the PGC-1s are essential effectors of epidermal physiology, revealing an axis that could be targeted in skin conditions and aging.

Identifiants

pubmed: 37009228
doi: 10.1016/j.isci.2023.106314
pii: S2589-0042(23)00391-7
pmc: PMC10064239
doi:

Types de publication

Journal Article

Langues

eng

Pagination

106314

Informations de copyright

© 2023 The Authors.

Déclaration de conflit d'intérêts

The authors have no competing interests to declare.

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Auteurs

Simon-Pierre Gravel (SP)

Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada.
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada.
Faculté de Pharmacie, Université de Montréal, Montréal, QC H3C 3J7, Canada.

Youcef Ben Khalifa (Y)

L'Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France.

Shawn McGuirk (S)

Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada.
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada.

Catherine St-Louis (C)

Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Karl M Laurin (KM)

Faculté de Pharmacie, Université de Montréal, Montréal, QC H3C 3J7, Canada.

Émilie Lavallée (É)

Faculté de Pharmacie, Université de Montréal, Montréal, QC H3C 3J7, Canada.

Damien Benas (D)

EPISKIN, 69366 Lyon Cedex 7, France.

Stéphanie Desbouis (S)

L'Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France.

Frédéric Amaral (F)

L'Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France.

Damien D'Amours (D)

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Lionel Breton (L)

L'Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France.

Sibylle Jäger (S)

L'Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France.

Julie St-Pierre (J)

Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada.
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada.
Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Classifications MeSH