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IL-22-mediated microRNA-124-3p/GRB2 axis regulates hyperproliferation and inflammatory response of keratinocytes in

Jiaqi Li1,2, Wenjuan Chang2, Junqin Li2

  • 1School of Public Health, Shanxi Medical University, Taiyuan, China.

Archives of Dermatological Research
|January 10, 2025
PubMed

Insights

Interleukin-22 (IL-22) triggers psoriasis by downregulating microRNA-124-3p (miR-124-3p), which increases growth factor receptor-bound protein 2 (GRB2) in skin cells. This leads to keratinocyte overproliferation and inflammation.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Immunology

Background:

  • Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation.
  • Interleukin-22 (IL-22) is implicated in psoriasis pathogenesis, potentially through microRNA regulation.
  • MicroRNAs can target multiple genes, suggesting miR-124 may influence other pathways in IL-22-induced keratinocyte dysfunction.

Purpose of the Study:

  • To investigate the role of miR-124-3p and its potential target, growth factor receptor-bound protein 2 (GRB2), in IL-22-mediated keratinocyte responses in psoriasis.
  • To elucidate the regulatory mechanism of GRB2 by miR-124-3p in keratinocytes.
  • To assess the impact of GRB2 on keratinocyte proliferation and inflammation.

Main Methods:

  • Bioinformatic screening identified GRB2 as a potential target of miR-124-3p.
  • Expression levels of GRB2 and miR-124-3p were analyzed in psoriatic lesions and control skin.
  • In vitro experiments used IL-22-stimulated HaCaT cells transfected with miR-124-3p mimics or GRB2 inhibitors.
  • Cell proliferation, inflammatory mediator expression, and protein levels (Ki67, PCNA, K16) were assessed.

Main Results:

  • GRB2 expression was elevated, while miR-124-3p was decreased in psoriatic lesions.
  • Overexpression of miR-124-3p in keratinocytes reduced GRB2 levels.
  • High GRB2 expression promoted keratinocyte proliferation and inflammatory markers; low GRB2 expression inhibited these effects.
  • GRB2 inhibition demonstrated a dose-dependent effect on keratinocyte proliferation and inflammation.
  • Overexpression of both GRB2 and miR-124-3p showed that miR-124-3p could reverse GRB2-induced hyperproliferation and inflammation.

Conclusions:

  • IL-22-mediated downregulation of miR-124-3p contributes to psoriasis by increasing GRB2 expression in keratinocytes.
  • GRB2 plays a significant role in promoting keratinocyte hyperproliferation and inflammatory responses in psoriasis.
  • Targeting the miR-124-3p/GRB2 axis represents a potential therapeutic strategy for psoriasis.
Keywords:
GRB2KeratinocyteMiR-124-3pPsoriasis

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