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J Invest Dermatol. 2018 Dec;138(12):2511-2521. doi: 10.1016/j.jid.2018.05.026. Epub 2018 Jun 12.

Dermal Fibroblast SLC3A2 Deficiency Leads to Premature Aging and Loss of Epithelial Homeostasis.

Author information

1
Institut de Recherche sur le Cancer et le Vieillissement, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Université Cote d'Azur, Nice, France.
2
Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Institut Paoli-Calmettes, Aix-Marseille Université, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Marseille, France.
3
Institut de Recherche sur le Cancer et le Vieillissement, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Université Cote d'Azur, Nice, France. Electronic address: chloe.feral@inserm.fr.

Abstract

Skin homeostasis relies on fine-tuning of epidermis-dermis interactions and is affected by aging. While extracellular matrix (ECM) proteins, such as integrins, are involved in aging, the molecular basis of the skin changes needs to be investigated further. Here, we showed that integrin co-receptor, SLC3A2, required for cell proliferation, is expressed at the surface of resting dermal fibroblasts in young patients and is reduced drastically with aging. In vivo SLC3A2 dermal fibroblast deletion induced major skin phenotypes resembling premature aging. Knockout mice (3 months old) presented strong defects in skin elasticity due to altered ECM assembly, which impairs epidermal homeostasis. SLC3A2 dermal fibroblast loss led to an age-associated secretome profile, with 77% of identified proteins belonging to ECM and ECM-associated proteins. ECM not only contributes to skin mechanical properties, but it is also a reservoir of growth factors and bioactive molecules. We demonstrate that dermal fibroblast SLC3A2 is required for ECM to fully exert its structural and reservoir role allowing proper and efficient TGF-β localization and activation. We identified SLC3A2 as a protective controller of dermal ECM stiffness and quality required to maintain the epidermis to dermis interface as functional and dynamic.

PMID:
29906411
DOI:
10.1016/j.jid.2018.05.026

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