Increased epidermal growth factor receptor in fsn/fsn mice.
Epidermal growth factor receptors (EGF-Rs) are elevated in active human psoriatic lesions, but decrease in resolving lesions. Similar biologic responses in EGF-R levels have been demonstrated within human psoriatic skin grafted onto mice. We tested the hypothesis that flaky-skin mice (fsn/fsn), one proposed genetic animal model of psoriasis, would display EGF-R levels comparable to human psoriatic epidermis and show similar biologic responses. EGF-R levels were characterized in unperturbed sites in fsn/fsn skin and +/? skin by enzyme-linked immunosorbent assay, 125I-EGF binding, and immunostaining. Altered EGF-R levels were noted after mild trauma (tape stripping) or under resolving conditions (30 doses of 50 mJ/CM2 ultraviolet B, 2.5 mg/kg oral cyclosporin A, or daily 30 microg/ml topical EGF). Increased EGF-R immunostaining was observed in involved flaky epidermal sites before treatment. To determine whether a hyperproliferative (Koebner) reaction could be induced, we tape stripped fsn/fsn tail and non-flaky dorsal sites. EGF-R levels in dorsal epidermis increased by days 3-4 after injury by enzyme-linked immunoabsorbent assay methods. When fsn/fsn mice received one of three different treatments for 6 weeks, the skin returned to a normal phenotype both grossly and microscopically. Immunoreactive EGF-R in treated, but not untreated, sites decreased to either normal or nondetectable levels. These data indicate that fsn/fsn mice exhibit an EGF-R profile identical to that of lesional and nonlesional human psoriatic epidermis. Modulations of the flaky phenotype in response to injury and three different treatments suggest that fsn/fsn is a useful in vivo model for examining new treatment modalities for psoriasiform skin diseases.
Nanney
L B
LB
Department of Plastic Surgery, Vanderbilt School of Medicine, Nashville, Tennessee, USA.
Sundberg
J P
JP
King
L E
LE
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000627:therapeutic use; D066246:ErbB Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics* / Q000378:metabolism*; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014466:Ultraviolet Rays; D014947:Wounds and Injuries / Q000378:metabolism
D004815:Epidermal Growth Factor; D016572:Cyclosporine; D066246:ErbB Receptors