Description
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.