Desmoglein-4 deficiency enhances skin lesions in a rat psoriasis model.

SANCHEZ MB; MORENO-SOSA MT; PIETROBON EO; INNOCENTI BADANO AC; JAHN GA; MACKERN OBERTI JP

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínicaa

Desmogleins are proteins involved in cell adhesion and structural integrity of different tissues. In skin, desmogleins modulate keratinocyte (KC) activation and may control key molecules that participate in signaling pathways. It is known that psoriasis is a chronic inflammatory skin disease, characterized by KC hyperproliferation, vasculature growth, and leukocyte infiltration into the dermis and epidermis. However, the role of desmoglein-4 in psoriasis development is unknown. Our aim was to assess the impact of desmoglein-4 deficiency in the histological structure of the skin. To this end, we used a rat psoriasis model using Imiquimod (IMQ), a TLR7 ligand that induces skin lesions closely resembling human psoriasis. IMQ was administered to the shaved skin for four days to generate psoriasis-like lesions in OFA hr/hr (desmoglein-4 deficient) and Sprague-Dawley (SD) rats. Skin biopsies from treated and untreated OFA and SD rats were processed to obtain histological sections that were dyed with hematoxylin/eosin. Histopathological analysis showed that IMQ treated OFA hr/hr rats displayed more severe changes in epidermis, dermis and sub-cutis with increased KC apoptosis compared with IMQ treated SD rats. Furthermore, lymphocytic perifollicular and perivascular infiltration and vasodilatation were more intense in IMQ-treated OFA rats than in SD rats. In contrast, adhesion molecules such as cadherin-VE, cadherin-N and cadherin-E qPCR analysis did not show changes between all experimental groups. These results suggest that desmoglein-4 deficiency contributes to experimental psoriasis development, promoting increased vasculature growth and leukocyte infiltration into the dermis and epidermis. Although further research is needed, these results could have a potential impact on prognostic and diagnostic parameters in psoriasis.