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

Gwendoline Degueurce (1) , Ilenia d'Errico (1) , Christine Pich (1) , Mark Ibberson (2) , Frédéric Schütz (1) , Alexandra Montagner (3) , Marie Sgandurra (1) , Lionel Mury (1) , Paris Jafari (4) , Akash Boda (1) , Julien Meunier (1) , Roger Rezzonico , Nicolò Costantino Brembilla , Daniel Hohl (5) , Antonios Kolios (6, 7) , Günther Hofbauer (7) , Ioannis Xenarios (2) , Liliane Michalik (1)

1 Faculty of Biology and Medicine, Center for Integrative Genomics
2 SIB - Swiss Institute of Bioinformatics [Lausanne]
3 ToxAlim - ToxAlim
4 Department of Musculoskeletal Medicine, Service of Plastic and Reconstructive Surgery
5 Service de dermatologie et venereology, Hôpital de Beaumont
6 Department of Immunology, University Hospital,
7 Department of Dermatology, University Hospital

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.

Mots clés: miRNA; skin; therapeutics; PPAR beta/delta; uv light

Mots clés: médecine humaine; inflammation; maladie de la peau; rayonnement ultraviolet

Domaines: Médecine humaine et pathologie

Gwendoline Degueurce, Ilenia d'Errico, Christine Pich, Mark Ibberson, Frédéric Schütz, et al.. Identification of a novel PPAR beta/delta/miR‐21‐3p axis in UV‐induced skin inflammation. EMBO Molecular Medicine, 2016, 8 (8), pp.919-936. ⟨10.15252/emmm.201505384⟩. ⟨hal-01594498⟩