Open AccessIdentification of a novel PPAR β/δ/miR‐21‐3p axis in UV ‐induced skin inflammation
Author(s) -
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
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505384
Subject(s) - library science , genomics , integrative medicine , medicine , biology , genetics , computer science , pathology , genome , gene , alternative medicine
Abstract Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPAR β/δ is known to control mouse cutaneous repair and UV ‐induced skin cancer development. Here, we describe a novel PPAR β/δ‐dependent molecular cascade involving TGF β1 and miR‐21‐3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger mi RNA miR‐21‐3p, that we identify as a novel UV ‐induced mi RNA in the epidermis, plays a pro‐inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR‐21‐3p reduces UV ‐induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of mi RNA ‐based topical therapies for cutaneous disorders.