HAX-1, identified by differential display reverse transcription polyerase chain reaction, is overexpressed in lesional psoriasis

Authors:
Mirmohammadsadegh A, Tartler U, Michel G, Baer A, Walz M, Wolf R, Ruzicka T and Hengge UR
In:
J Invest Dermatol (2003) 120: 1045-1051
Cells used in publication:
HaCaT
Species: human
Tissue Origin: dermal
Experiment
Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and an inflammatory infiltrate. A number of studies lead to the hypothesis that a disturbed apoptosis might be involved in the etiology of the disease. The authors found HAX-1 to be overexpressed in lesional psoriatic skin and the immortalized HaCaT cell line. The authors studied the antiapoptotic function of HAX-1 by nucleofecting HaCaT cells with an expression vector for HAX-1 sense or antisense mRNA expression. After UVB irradiation apoptotic activity was determine by a caspase-3 assay. The results strongly suggested an antiapoptotic role of HAX-1.
Abstract
Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and an inflammatory infiltrate. The normal differentiation from basal to granular keratinocytes with subsequent apoptosis and cornification is disturbed in the akanthotic epidermis. This could be due to both an excess of mitogenic stimuli with hyperproliferation and/or resistance to apoptosis. By mRNA differential display we found HAX-1 to be overexpressed in lesional psoriatic skin. The overexpression of HAX-1 was verified at the mRNA level by Northern blot and in situ hybridization, as well as at the protein level by Western blot and immunohistochemistry. Detection of HAX-1 in mRNA from different tissues showed strong expression in the brain, pancreas, skeletal muscle, and heart. In contrast to primary keratinocytes and melanocytes we found HAX-1 highly expressed in human immortalized keratinocytes (HaCaT) and different melanoma cell lines. In HaCaT cells as a model for psoriatic keratinocytes we found an increased ultraviolet-induced apoptosis after expression of HAX-1 antisense mRNA. In psoriasis, the epidermal differentiation could be disturbed due to the increased expression of HAX-1 and hence a prolonged resistance to terminal differentiation. Antiapoptotic mechanisms are an emerging concept for the understanding of the pathogenesis of this disease possibly leading to clinical applications.