Overexpression of the oncofetal Fn variant containing the EDA splice-in segment in the dermal-epidermal junction of psoriatic uninvolved skin

The extracellular matrix protein, Fn, has critical functions in cell attach ment, migration, differentiation, and proliferation. We have previously sho wn that fibronectin (Fn) is abnormally expressed and potentiates entry into the cell cycle of basal keratinocytes in uninvolved psoriatic skin, in com bination with T cell lymphokines. It is not known what type of Fn is presen t in psoriatic skin, however, and how this Fn may regulate signaling. Embry onic forms of cellular Fn containing extra domains, designated EDA and EDB, are generated by alternative splicing and are seen in proliferating, devel oping tissue and in wound healing. Because the EDA segment enhances the int egrin binding sequence Arg, Gly, Asp (RGD), which, when present, has been s hown to be critical in integrin-extracellular matrix signaling, we were par ticularly interested in determining whether or not EDA-containing Fn (EDA()Fn) represented the aberrantly expressed Fn in psoriasis. Increased EDA(+) Fn protein was demonstrated by immunostaining at the dermal-epidermal junc tion in clinically uninvolved skin from six of six patients with psoriasis, but not in skin from control subjects. Using reverse transcription polymer ase chain reaction an increased ratio of EDA(+) Fn versus EDA(-) Fn mRNA wa s present in epidermal samples from psoriatic but not control individuals. Interestingly, the EDA(+)Fn in the psoriatic epidermis had the IIICS region spliced out (EDA(+), FDB-, IIICS-, III9(+)), which was shared with normal epidermis (EDA(-), EDB-, IIICS-, III9(+)). These results suggest a selectiv e predominance of the EDA(+) Fn isoform at the dermal-epidermal junction of psoriatic skin. The consistent aberrant localization of EDA(+) Fn at the d ermal-epidermal junction in uninvolved skin of psoriatics may confer the hy perresponsiveness of psoriatic uninvolved basal keratinocytes for rapid cel lular proliferation in response to T cell signals. Key words: immunohistoch emistry/integrin/keratinocyte/RT-PCR.