Psoriasis is a heterogeneous disease in which a relatively large number of patients exhibit epidermal hyperproliferation and therapeutic responsiveness to relatively low doses of methotrexate (MTX). Our recent studies have revealed folate receptors to mediate cellular uptake of MTX through a newly characterized form of receptor-mediated endocytosis, called """"""""potocytosis"""""""". We have also shown these folate receptors to promote keratinocyte proliferation in the presence of physiologic concentrations of folate. We thus hypothesize hyperproliferation of keratinocytes in some patients with psoriasis to be due, at least in part, to overexpression and/or altered function of folate receptors on these cells, a finding that may also explain the extreme sensitivity of such patients to MTX. This hypothesis will be tested by analyzing expression and potocytotic activity of folate receptors on psoriatic keratinocytes.
Specific aims are: l) to demonstrate folate receptor expression on keratinocytes from psoriatic skin, 2) to establish cultures of keratinocytes from psoriatic skin grown in physiologic concentrations of folate, 3) to characterize the function of folate receptors in these lines, and 4) to develop an in vitro model of the hyperproliferative and MTX-responsive form of psoriasis.
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