PGC-1s shape epidermal physiology by modulating keratinocyte proliferation and terminal differentiation
Simon-Pierre Gravel,
Youcef Ben Khalifa,
Shawn McGuirk,
Catherine St-Louis,
Karl M. Laurin,
Émilie Lavallée,
Damien Benas,
Stéphanie Desbouis,
Frédéric Amaral,
Damien D’Amours,
Lionel Breton,
Sibylle Jäger,
Julie St-Pierre
Affiliations
Simon-Pierre Gravel
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; Corresponding author
Youcef Ben Khalifa
L’Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France
Shawn McGuirk
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
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
Faculté de Pharmacie, Université de Montréal, Montréal, QC H3C 3J7, Canada
Émilie Lavallée
Faculté de Pharmacie, Université de Montréal, Montréal, QC H3C 3J7, Canada
Damien Benas
EPISKIN, 69366 Lyon Cedex 7, France
Stéphanie Desbouis
L’Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France
Frédéric Amaral
L’Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France
Damien D’Amours
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’Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France
Sibylle Jäger
L’Oréal Research & Innovation, 93600 Aulnay-sous-Bois, France
Julie St-Pierre
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; Corresponding author
Summary: 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.
