Work

Vascular Endothelial Growth Factor a Inhibition Remodels the Transcriptional Signature of Lipid Metabolism in Psoriasis Non-Lesional Skin in 12 H Ex Vivo Culture

Year: 2024

Type: article

Abstract: Background Vascular endothelial growth factor A (VEGF-A)-mediated angiogenesis is involved in the pathogenesis of psoriasis. VEGF-A inhibitors are widely used to treat oncological and ophthalmological diseases but have not been used in psoriasis management. The molecular mechanisms underlying the effects of VEGF-A inhibition in psoriatic skin remain unknown. Objectives To identify the genes and canonical pathways affected by VEGF-A inhibition in non-lesional and plaque skin ex vivo. Methods Total RNA sequencing was performed on skin biopsies from patients with psoriasis (n = 6; plaque and non-lesional skin) and healthy controls (n = 6) incubated with anti-VEGF-A monoclonal antibody (bevacizumab, Avastin®) or human IgG1 isotype control for 12 h in serum-free organ culture. Differentially expressed genes between paired control and treated samples with adjusted p-values <0.1 were considered significant. Gene ontology and ingenuity pathway analysis was used to identify enriched biological processes, canonical pathways and upstream regulators. Results VEGF-A inhibition upregulated the expression of genes involved in lipid metabolism. Pathway enrichment analysis identified the activation of pathways involved in fatty acids and lipid biosynthesis and degradation in non-lesional skin and ferroptosis in plaque skin. VEGF-A inhibition downregulated endothelial cell apoptosis in non-lesional psoriasis skin and members of the interferon family were identified as potential regulators of the effects of VEGF-A inhibition in non-lesional skin. Conclusion Early response to VEGF-A inhibition is associated with changes in lipid metabolism in non-lesional psoriasis skin and cellular stress in psoriasis plaque. More investigation is needed to validate these findings.

Source: Skin Health and Disease

DOI: 10.1002/ski2.471

Authors: Andrea Luengas-Martinez, Dina Ismail, Ralf Paus, Helen S. Young

Institutions: Manchester Academic Health Science Centre, University of Manchester, University of Miami

Language: English

Topic: Psoriasis: Treatment and Pathogenesis

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,403