title: AMPK/HuR-Driven IL-20 Post-Transcriptional Regulation in Psoriatic Skin.
abstract: IL-20 is involved in the development of skin psoriasis. The molecular mechanisms underlying IL-20 overexpression in psoriatic epidermis remain to be elucidated. We showed that IL-20 was primarily upregulated in psoriatic skin at the post-transcriptional level. The RNA-binding protein HuR relocalized to the cytoplasm of keratinocytes (KCs) of psoriatic patients, suggesting that it stabilizes numerous transcripts, as observed in the human KC cell lines used to assess IL-20 mRNA. We characterized epidermal HuR RNA targets in psoriatic skin using ribonucleoprotein immunoprecipitation analyzed via high-throughput sequencing. Numerous transcripts that are upregulated in psoriasis were targeted by HuR, supporting the participation of HuR in pathogenic processes such as morphological changes, innate and adaptive immune responses, and metabolic inflammatory responses. Finally, we identified the metabolic sensor AMP-activated protein kinase (AMPK) as being responsible for HuR cytoplasmic relocalization because its activity was severely impaired in human psoriatic epidermis, and in vivo drug-mediated AMPK inhibition in mouse epidermis promoted HuR cytoplasmic localization, IL-20 overproduction, acanthosis, and hyperkeratosis. These results provide insights into the molecular links between metabolism and post-transcriptional networks during chronic inflammation.
authors.affiliation: Dynamique des Interactions Membranaires Normales et Pathologiques (DIMNP), CNRS UMR 5235, Université de Montpellier, Montpellier, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Garcin
authors.affiliation: Laboratoire d'Histologie-Embryologie-Cytogénétique, Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Faculté de Médecine Montpellier-Nîmes, Université de Montpellier, Nîmes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guiraud
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier (IRCM), Institut régional du Cancer Montpellier (ICM), INSERM U896, Université de Montpellier, Montpellier, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lacroix
authors.affiliation: Montpellier Genomix (MGX), Institut de Génomique Fonctionnelle (IGF), CNRS INSERM UMS3426, Université de Montpellier, Montpellier, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Genthon
authors.affiliation: Montpellier Genomix (MGX), Institut de Génomique Fonctionnelle (IGF), CNRS INSERM UMS3426, Université de Montpellier, Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rialle
authors.affiliation: Service d'Anatomopathologie, Centre Hospitalier Universitaire de Nîmes, Nîmes, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Joujoux
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire de Nîmes, Nîmes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Meunier
authors.affiliation: Laboratoire d'Histologie-Embryologie-Cytogénétique, Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Faculté de Médecine Montpellier-Nîmes, Université de Montpellier, Nîmes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lavabre-Bertrand
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire de Nîmes, Nîmes, France. Electronic address: lionel.le-gallic@univ-montp1.fr.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Stoebner
authors.affiliation: Laboratoire d'Histologie-Embryologie-Cytogénétique, Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Faculté de Médecine Montpellier-Nîmes, Université de Montpellier, Nîmes, France. Electronic address: lionel.le-gallic@univ-montp1.fr.
authors.forename: Lionel
authors.initials: L
authors.lastname: Le Gallic
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001707:Biopsy, Needle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000166:cytology / Q000473:pathology; D018709:Statistics, Nonparametric; D015854:Up-Regulation
chemical_list: D000067780:ELAV-Like Protein 1; D007378:Interleukins; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases; C422042:interleukin 20