title: Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.
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 PPARβ/δ is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ1 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.
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Degueurce
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Ilenia
authors.initials: I
authors.lastname: D'Errico
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Pich
authors.affiliation: SIB Swiss Institute of Bioinformatics University of Lausanne, Lausanne, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Ibberson
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland SIB Swiss Institute of Bioinformatics University of Lausanne, Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Schütz
authors.affiliation: INRA ToxAlim, Integrative Toxicology and Metabolism, UMR1331, Toulouse, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Montagner
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Sgandurra
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Lionel
authors.initials: L
authors.lastname: Mury
authors.affiliation: Department of Musculoskeletal Medicine, Service of Plastic and Reconstructive Surgery CHUV, Epalinges, Switzerland.
authors.forename: Paris
authors.initials: P
authors.lastname: Jafari
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Akash
authors.initials: A
authors.lastname: Boda
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Meunier
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UMR 7275, Valbonne, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Rezzonico
authors.affiliation: Dermatology, University Hospital and School of Medicine, Geneva, Switzerland Immunology and Allergy, University Hospital and School of Medicine, Geneva Switzerland.
authors.forename: Nicolò Costantino
authors.initials: NC
authors.lastname: Brembilla
authors.affiliation: Service de dermatologie et venereology, Hôpital de Beaumont CHUV, Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.affiliation: Department of Immunology, University Hospital, University of Zürich, Zürich, Switzerland Department of Dermatology, University Hospital, University of Zürich, Zürich, Switzerland.
authors.forename: Antonios
authors.initials: A
authors.lastname: Kolios
authors.affiliation: Department of Dermatology, University Hospital, University of Zürich, Zürich, Switzerland.
authors.forename: Günther
authors.initials: G
authors.lastname: Hofbauer
authors.affiliation: SIB Swiss Institute of Bioinformatics University of Lausanne, Lausanne, Switzerland.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Xenarios
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland liliane.michalik@unil.ch.
authors.forename: Liliane
authors.identifier: 0000-0003-2963-2100
authors.initials: L
authors.lastname: Michalik
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism*; D011855:Radiodermatitis / Q000473:pathology*; D015398:Signal Transduction; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D047494:PPAR delta; D048068:PPAR-beta
keywords: PPARβ/δ; inflammation; miRNA; skin; therapeutics