Identification of a novel PPAR beta/delta/miR‐21‐3p axis in UV‐induced skin inflammation

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Degueurce, Gwendoline | d'Errico, Ilenia | Pich, Christine | Ibberson, Mark | Schütz, Frédéric | Montagner, Alexandra | Sgandurra, Marie | Mury, Lionel | Jafari, Paris | Boda, Akash | Meunier, Julien | Rezzonico, Roger | Brembilla, Nicolò Costantino | Hohl, Daniel | Kolios, Antonios | Hofbauer, Günther | Xenarios, Ioannis | Michalik, Liliane

Edité par CCSD ; Wiley Open Access -

Although excessive exposure to UV is widely recognized as a majorfactor leading to skin perturbations and cancer, the complex mech-anisms underlying inflammatory skin disorders resulting from UVexposure remain incompletely characterized. The nuclear hormonereceptor PPARb/d is known to control mouse cutaneous repair andUV-induced skin cancer development. Here, we describe a novelPPARb/d-dependent molecular cascade involving TGFb1 and miR-21-3p, which is activated in the epidermis in response to UV expo-sure. We establish that the passenger miRNA miR-21-3p, that weidentify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level ofexpression in human skin is associated with psoriasis and squa-mous cell carcinomas. Finally, we provide evidence that inhibitionof miR-21-3p reduces UV-induced cutaneous inflammation inex vivo human skin biopsies, thereby underlining the clinical rele-vance of miRNA-based topical therapies for cutaneous disorders.

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