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

EMBO Mol Med. 2016 Aug 1;8(8):919-36. doi: 10.15252/emmm.201505384. Print 2016 Aug.


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.

Keywords: PPARβ/δ; inflammation; miRNA; skin; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • PPAR delta / metabolism*
  • PPAR-beta / metabolism*
  • Radiodermatitis / pathology*
  • Signal Transduction*
  • Skin / radiation effects*
  • Ultraviolet Rays*


  • MIRN21 microRNA, human
  • MicroRNAs
  • PPAR delta
  • PPAR-beta