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Aberrant signalling and transcription factor activation as an explanation for the defective growth control and differentiation of keratinocytes in psoriasis: a hypothesis
Author(s) -
McKenzie R. C.,
Sabin E.
Publication year - 2003
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1034/j.1600-0625.2003.00100.x
Subject(s) - psoriasis , transcription factor , stat protein , microbiology and biotechnology , activator (genetics) , receptor , biology , signal transduction , immunology , genetics , stat3 , gene
Abstract: Psoriasis is a chronic inflammatory skin disease characterized by the accumulation of red, scaly plaques on the skin. The plaques result from hyperproliferation and incomplete differentiation of keratinocytes (KC) in a process that seems to be driven, in part by skin‐infiltrating leucocytes. We believe that the KC have inherent defects in intracellular signalling which could be usefully targeted to allow the development of more effective therapies. We suggest that there are defects in the regulation of the transcription factors: signal transducer and activator of transcription (STAT‐1α), interferon regulated factor‐1 (IRF‐1) and NFκB which lead to loss of growth and differentiation control when the cells are subjected to physico‐chemical and immunological stress. We also highlight recent studies that suggest that peroxisome proliferator‐activated receptors, the notch receptor and defects in calcium and other ion transporting proteins may contribute to impairment in the ability of psoriatic KC to differentiate. The role of these systems in the development of the psoriatic phenotype and tests of these hypotheses are proposed.