Biological therapy induces expression changes in Notch pathway in psoriasis

Evangelia Skarmoutsou1, Chiara Trovato1, Mariagrazia Granata1

  • 1Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.

Insights

This study investigated the Notch pathway in psoriasis, finding its components upregulated in patients. Biological treatments for psoriasis downregulated these Notch pathway molecules, suggesting they are potential therapeutic targets.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Immunology

Background:

  • Psoriasis is a chronic inflammatory skin disease driven by keratinocyte hyperproliferation and T-cell infiltration.
  • The precise pathophysiology of psoriasis remains incompletely understood.
  • The Notch pathway is crucial for cell fate, proliferation, differentiation, and immune function.

Purpose of the Study:

  • To investigate the expression of Notch pathway components (NOTCH1, NOTCH2, JAGGED1, HES1) in psoriatic skin.
  • To analyze the impact of biological therapies on Notch pathway component expression in psoriasis patients.

Main Methods:

  • Real-time RT-PCR was used to quantify mRNA expression levels.
  • Western blot and immunohistochemistry were employed to assess protein expression levels.
  • Skin samples from untreated psoriatic patients and normal controls were analyzed, along with samples post-biological treatment.

Main Results:

  • mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1, and HES1 were significantly upregulated in untreated psoriatic skin compared to normal controls.
  • Biological therapies demonstrated varied downregulation effects on the protein expression of these Notch pathway molecules.
  • Specific biological agents evaluated included TNF-α inhibitors and anti-IL-12/IL-23 p40 antibodies.

Conclusions:

  • Components of the Notch pathway are upregulated in psoriatic skin.
  • Biological treatments modulate the expression of Notch pathway molecules in psoriasis.
  • The Notch pathway represents a potential therapeutic target for managing psoriasis.

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