miR‑155 promotes an inflammatory response in HaCaT cells via the IRF2BP2/KLF2/NF‑κB pathway in psoriasis

Lu Chen1, Chang Liu1, Xuesong Xiang1

  • 1Department of Immunology, School of Medicine, Jianghan University, Wuhan, Hubei 430056, P.R. China.

Insights

MicroRNA-155 (miR-155) exacerbates psoriasis by promoting inflammation through the IRF2BP2/KLF2/NF-κB pathway. Inhibiting miR-155 may offer a therapeutic strategy for psoriasis by reducing inflammatory responses.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Immunology

Background:

  • Psoriasis is a chronic inflammatory skin disease with complex pathogenesis.
  • Aberrant microRNA (miRNA) expression, particularly miR-155, is linked to psoriasis development.
  • The precise molecular mechanisms underlying miR-155's role in psoriatic inflammation require further elucidation.

Purpose of the Study:

  • To investigate the role of differentially expressed genes and miRNAs in psoriasis.
  • To analyze the biological mechanisms and functions of miR-155 in psoriatic inflammation.
  • To explore the potential therapeutic targeting of miR-155 in psoriasis.

Main Methods:

  • Bioinformatic analysis of gene and miRNA expression data in psoriasis patients.
  • Establishment of a lipopolysaccharide (LPS)-induced HaCaT keratinocyte model for psoriasis.
  • Transfection with miR-155 mimic or inhibitor, followed by cell viability, cell cycle, inflammatory cytokine (IL-1β, IL-6) assays, and dual-luciferase reporter assays.
  • Validation of the miR-155 targeting of IRF2BP2 and its downstream effects on the IRF2BP2/KLF2/NF-κB pathway using RT-qPCR, western blotting, and immunofluorescence.

Main Results:

  • Overexpression of miR-155 inhibited HaCaT cell proliferation and altered cell cycle distribution.
  • In LPS-treated cells, miR-155 overexpression intensified inflammation, while inhibition reduced it.
  • miR-155 directly targets IRF2BP2, leading to decreased KLF2 and increased p65 expression, thereby promoting inflammatory responses via the IRF2BP2/KLF2/NF-κB pathway.
  • Knockdown of IRF2BP2 reversed the anti-inflammatory effects of miR-155 inhibition.

Conclusions:

  • miR-155 plays a significant role in promoting psoriatic inflammation by negatively regulating IRF2BP2 expression.
  • The miR-155/IRF2BP2/KLF2/NF-κB axis is a key pathway contributing to psoriasis pathogenesis.
  • Targeting miR-155 presents a potential therapeutic strategy for managing psoriasis by mitigating inflammation and tissue damage.

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