miR‑203 contributes to IL‑17‑induced VEGF secretion by targeting SOCS3 in keratinocytes

Mol Med Rep. 2017 Dec;16(6):8989-8996. doi: 10.3892/mmr.2017.7759. Epub 2017 Oct 10.

Abstract

Interleukin (IL)-17 signaling serves an important role in the development and pathogenesis of psoriasis; a chronic skin disease characterized by increased dermal vascularity and the hyperproliferation of keratinocytes. microRNA (miR)‑203 is preferentially expressed in the skin and is an important regulator of keratinocyte differentiation. miR‑203 has been implicated in a number of skin diseases, including psoriasis. However, the role of miR‑203 in IL‑17‑induced vascular endothelial growth factor (VEGF) secretion has yet to be elucidated. The present study demonstrated that miR‑203 expression was upregulated in the ears of IL‑17‑stimulated mice and IL‑17‑treated HaCaT cells. In addition, the IL‑17‑induced increase in miR‑203 expression activated the Janus kinase/signal transducer and activator of transcription signaling pathway and promoted VEGF secretion in HaCaT cells. Furthermore, miR‑203 was observed to bind to the 3'‑untranslated region of suppressor of cytokine signaling 3 (SOCS3) and inhibited SOCS3 expression. The results suggest that miR‑203 expression may be upregulated by IL‑17 stimulation, and miR‑203 is a positive regulator of IL‑17‑induced VEGF secretion. The present study may support potential therapeutic strategies for the treatment of psoriasis.

MeSH terms

  • Animals
  • Base Sequence
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Interleukin-17 / pharmacology*
  • Janus Kinase 2 / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling 3 Protein / metabolism*
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Interleukin-17
  • MIRN203 microRNA, human
  • MIRN203 microRNA, mouse
  • MicroRNAs
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Vascular Endothelial Growth Factor A
  • Janus Kinase 2