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

被引：44

作者：

Degueurce, Gwendoline ^{[1
]}

D'Errico, Ilenia ^{[1
]}

Pich, Christine ^{[1
]}

Ibberson, Mark ^{[2
]}

Schutz, Frederic ^{[1
,2
]}

Montagner, Alexandra ^{[3
]}

Sgandurral, Marie ^{[1
]}

Muryl, Lionel ^{[1
]}

Jafari, Paris ^{[4
]}

Bodal, Akash ^{[1
]}

Meunier, Julien ^{[1
]}

Rezzonico, Roger ^{[5
]}

Brembilla, Nicolo Costantino ^{[6
,7
,8
]}

Hohl, Daniel ^{[9
]}

Kolios, Antonios ^{[10
,11
]}

Hofbauer, Gunther ^{[11
]}

Xenarios, Loannis ^{[2
]}

Michalik, Liliane ^{[1
]}

机构：

[1] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, Lausanne, Switzerland

[2] Univ Lausanne, SIB, Lausanne, Switzerland

[3] INRA ToxAlim, Integrat Toxicol & Metab, UMR1331, Toulouse, France

[4] CHUV, Serv Plast & Reconstruct Surg, Dept Musculoskeletal Med, Epalinges, Switzerland

[5] CNRS, Inst Pharrnacol Mol & Cellulaire, UMR 7275, Valbonne, France

[6] Univ Hosp Geneva, Dermatol, Geneva, Switzerland

[7] Sch Med, Geneva, Switzerland

[8] Univ Hosp Geneva, Immunol & Allergy, Geneva, Switzerland

[9] CHU Vaudois, Hop Beaumont, Serv Dermatol & Venereol, Lausanne, Switzerland

[10] Univ Zurich, Univ Hosp, Dept Immunol, Zurich, Switzerland

[11] Univ Zurich, Univ Hosp, Dept Dermatol, Zurich, Switzerland

来源：

EMBO MOLECULAR MEDICINE | 2016年 / 8卷 / 08期

关键词：

inflammation; miRNA; PPAR beta/delta; skin; therapeutics; PROLIFERATOR-ACTIVATED RECEPTORS; SQUAMOUS-CELL CARCINOMAS; GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR; PPAR-BETA/DELTA; ULTRAVIOLET-RADIATION; ATOPIC-DERMATITIS; EXPRESSION; MICRORNAS; INDUCTION;

D O I：

10.15252/emmm.201505384

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 beta/delta is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPAR beta/delta-dependent molecular cascade involving TGF beta 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.

引用

页码：919 / 936

页数：18

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