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Published on: February 28, 2017
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.
Abstract:
Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.
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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