Altered [125I]epidermal growth factor binding and receptor distribution in psoriasis.
Stimulation of growth and differentiation of human epidermis by epidermal growth factor (EGF) is mediated by its binding to specific receptors. Whether EGF receptors primarily mediate cell division or differentiation in hyperproliferative disease such as psoriasis vulgaris is unclear. To study the pathogenesis of psoriasis, 4-mm2 punch biopsy specimens of normal, uninvolved, and involved psoriatic skin were assayed for EGF receptors by autoradiographic, immunohistochemical, and biochemical methods. Using autoradiographic and immunohistochemical methods, basal keratinocytes were found to contain the greatest number of EGF binding sites and immunoreactive receptors as compared to the upper layers of the epidermis in both normal epidermis and psoriatic skin. No EGF receptor differences between normal and psoriatic epidermis were observed in this layer. In the upper layers of the epidermis, a 2-fold increase in EGF binding capacity was observed in psoriatic skin as compared with normal thin or thick skin. Biochemical methods indicated that [125I]EGF binding was increased in psoriatic epidermis as compared with similar thickness normal epidermis when measured on a protein basis. Epidermal growth factor was shown to increase phosphorylation of the EGF receptor in skin. EGF receptors retained in the nonmitotic stratum spinosum and parakeratotic stratum corneum may reflect the incomplete, abnormal differentiation that occurs in active psoriatic lesions. Alternatively, retained EGF receptors may play a direct role in inhibiting cellular differentiation in the suprabasal layers.
D001345:Autoradiography; D004247:DNA / Q000032:analysis; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011565:Psoriasis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D012867:Skin / Q000378:metabolism
D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases