Gravel Simon-Pierre, Ben Khalifa Youcef, McGuirk Shawn, St-Louis Catherine, Laurin Karl M, Lavallée Émilie, Benas Damien, Desbouis Stéphanie, Amaral Frédéric, D'Amours Damien, Breton Lionel, Jäger Sibylle, St-Pierre Julie
Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada.
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada.
iScience. 2023 Mar 2;26(4):106314. doi: 10.1016/j.isci.2023.106314. eCollection 2023 Apr 21.
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.
皮肤在全身生理过程中发挥着核心作用，并且在衰老过程中会发生显著的功能变化。过氧化物酶体增殖物激活受体γ共激活因子（PGC-1）家族成员（PGC-1s）是众多组织生物学的关键调节因子，但我们对它们对皮肤功能的影响知之甚少。角质形成细胞中的全基因组表达谱分析和基因沉默发现，PGC-1s控制代谢基因的表达以及终末分化程序的表达。谷氨酰胺成为促进线粒体呼吸、角质形成细胞增殖以及PGC-1s和终末分化程序表达的关键底物。重要的是，PGC-1s的基因沉默降低了重建的有活力的人表皮替代物的厚度。角质形成细胞暴露于水杨酸衍生物会增强PGC-1s和终末分化基因的表达，并增加线粒体呼吸。总体而言，我们的结果表明，PGC-1s是表皮生理的重要效应因子，揭示了一个可在皮肤疾病和衰老中作为靶点的轴。
