Identification of a novel PPAR/ / miR-21-3p axis in UV-induced skin inflammation [mouse mRNA]

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/ is known to control cutaneous repair and UV-induced cancer development. Here, we describe a novel PPAR/-dependent molecular cascade involving TGF-1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA 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 miRNA-based topical therapies for cutaneous disorders.

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Degueurce G, D'Errico I, Pich C, Ibberson M, Schütz F, Montagner A, Sgandurra M, Mury L, Jafari P, Boda A, Meunier J, Rezzonico R, Brembilla NC, Hohl D, Kolios A, Hofbauer G, Xenarios I, Michalik L