Dermal Fibroblast SLC3A2 Deficiency Leads to Premature Aging and Loss of Epithelial Homeostasis - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Journal of Investigative Dermatology Année : 2018

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

Floriane S. Tissot
  • Fonction : Auteur
Soline Estrach
  • Fonction : Auteur
Etienne Boulter
  • Fonction : Auteur
Laurence Cailleteau
  • Fonction : Auteur
Lionel Tosello
  • Fonction : Auteur
Laetitia Seguin
Sabrina Pisano
Olivier Croce
Chloe C. Feral
  • Fonction : Auteur

Résumé

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-beta 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.

Dates et versions

hal-02143629 , version 1 (29-05-2019)

Identifiants

Citer

Floriane S. Tissot, Soline Estrach, Etienne Boulter, Laurence Cailleteau, Lionel Tosello, et al.. Dermal Fibroblast SLC3A2 Deficiency Leads to Premature Aging and Loss of Epithelial Homeostasis. Journal of Investigative Dermatology, 2018, 138 (12), pp.2511-2521. ⟨10.1016/j.jid.2018.05.026⟩. ⟨hal-02143629⟩
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