The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated...

Insulin-like growth factor I (IGF-I)/somatomedin C is an important mediator of keratinocyte growth in vitro, and the expression of IGF-I receptors in the basal layer of normal epidermis suggests that this growth pathway may function in the regulation of keratinocyte growth in vivo as well. The pattern of IGF-I receptor expression in normal skin is distinct from that of the epidermal growth factor (EGF) receptor, suggesting that these receptors might be differentially regulated. The purpose of this study was to obtain a better understanding of IGF-I receptor function in the skin by examining IGF-I receptor expression in psoriatic epidermis and in cultured human keratinocytes. Our findings indicate that IGF-I receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF-I receptor-specific monoclonal antibody. Unlike EGF receptor expression, which is also increased in psoriatic epidermis, the pattern of IGF-I receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis. Biochemical agents that diminish EGF receptor ligand binding (phorbol ester or calcium ionophore treatment) produce opposite effects on the IGF-I receptor. These results suggest that cellular expression and differential regulation of both growth factor receptor systems may control critical aspects of epidermal proliferation or function.