IQGAP proteins mediate many processes important for the development of hyperproliferative skin diseases, namely the EGF signaling, WNT and MAPK kinase cascades, they are required for cell adhesion and migration processes, tight junction and zonula occludens formation, cell cycle regulation. However, the possible contribution of the IQGAP3 in the development of hyperproliferative psoriatic plaques is unknown. We have shown earlier that IQGAP3 is overexpressed in the lesional skin of patients with psoriasis. Next we have performed the keratinocyte stimulation with proinflammatory cytokines associated with the development of psoriatic plaques (TNF alpha or a mix of IL-17+TNF alpha+IFN gamma in physiological concentrations) or with non-specific skin irritant 12-O-tetradecanoylphorbol-13-acetate (TPA) or with the EGF growth factor. We have shown that 24h later both the proinflammatory cytokines and EGF stimulation led to the moderate elevation of the IQGAP3expression (1,6 and 1,8 times respectively, p<0.05) unlike the TPA stimulation, which haven't led to any significant alterations in the IQGAP3 expression. As we have earlier identified FRA1, one of the AP1 transcription factors, to mediate keratinocyte activation in psoriasis, we were interested in the identification of a possible link to the IQGAP3 expression. Using a stable keratinocyte line overexpressing FRA1, we have shown that both the FRA1 overexpression itself or the overexpression under the proinflammatory conditions (IL-17+TNF alpha+IFN gamma stimulation) have led to the elevated expression of the IQGAP3 (3 and 4.8 times respectively, p<0.05). Thus the IQGAP3 overexpression in psoriatic plaques could be the consequence of the FRA1 overexpression under the proinflammatory conditions present in skin of patients with psoriasis. The research was supported by RSF (project 18-75-00126).

IQGAP proteins in psoriasis: is it only about scaffold?