Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation

Autor: Nicolò C. Brembilla, Julien Meunier, Ioannis Xenarios, Marie Sgandurra, Frédéric Schütz, Lionel Mury, Akash Boda, Günther F.L. Hofbauer, Mark Ibberson, Daniel Hohl, Roger Rezzonico, Alexandra Montagner, Gwendoline Degueurce, Antonios G.A. Kolios, Paris Jafari, Liliane Michalik, Ilenia D'Errico, Christine Pich
Přispěvatelé: Faculty of Biology and Medicine, Center for Integrative Genomics, Université de Lausanne, SIB Swiss Institute of Bioinformatics, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Department of Musculoskeletal Medicine, Service of Plastic and Reconstructive Surgery, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de dermatologie et venereology, Hôpital de Beaumont, Department of Immunology, University Hospital, University of Zurich, Department of Dermatology, University Hospital, This study was supported by FNRS Sinergia grant (26073695 CRSI33-130576 grant to Dr. L. Michalik and Prof. W. Wahli), University of Lausanne Herbette and UNIL Foundations (grants 26078145, 26078149 to Dr. L. Michalik), and by the Etat de Vaud, InnoPACTT (grant to Dr. G. Degueurce)., Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Michalik, Liliane
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
médecine humaine
Human skin
Mice
PPARβ/δ
therapeutics
PPAR delta
Research Articles
maladie de la peau
PPAR beta/delta
3. Good health
inflammation
miRNA
skin
Molecular Medicine
Peroxisome proliferator-activated receptor delta
Signal transduction
medicine.symptom
Radiodermatitis
Research Article
Signal Transduction
Ultraviolet Rays
Immunology
Médecine humaine et pathologie
610 Medicine & health
Inflammation
Biology
03 medical and health sciences
Psoriasis
medicine
Animals
Humans
uv light
Pharmacology & Drug Discovery
PPAR-beta
Epidermis (botany)
Cancer
medicine.disease
MicroRNAs
030104 developmental biology
rayonnement ultraviolet
1313 Molecular Medicine
10033 Clinic for Immunology
Cancer research
Human health and pathology
Skin cancer
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: EMBO Molecular Medicine, vol. 8, no. 8, pp. 919-936
EMBO Molecular Medicine
EMBO Molecular Medicine, Wiley Open Access, 2016, 8 (8), pp.919-936. ⟨10.15252/emmm.201505384⟩
Europe PubMed Central
EMBO Molecular Medicine 8 (8), 919-936. (2016)
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201505384⟩
Popis: 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.
Databáze: OpenAIRE
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