HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis.
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.
Mirmohammadsadegh
Alireza
A
Department of Dermatology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. a.sadegh@uni-duesseldorf.de
Tartler
Ulrike
U
Michel
Günter
G
Baer
Annett
A
Walz
Markus
M
Wolf
Ronald
R
Ruzicka
Thomas
T
Hengge
Ulrich R
UR
D048868:Adaptor Proteins, Signal Transducing; D015152:Blotting, Northern; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; C104759:HAX1 protein, human; D011506:Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases