Suprabasal overexpression of the hsRPB7 gene in psoriatic epidermis as identified by a reverse transcriptase-polymerase chain reaction differential display model comparing psoriasis plaque tissue with peritonsillar mucosa.
In psoriasis an etiopathogenetic vicious circle is nowadays hypothesized that the disease is triggered by skin-specific autoantigen structures, the expression and accessibility of which are positively correlated with the intensity of the hyperproliferation and inflammation in the epidermopapillary compartment driven by autoreactive T cells. Despite the close microanatomical relation between skin and mucosa, clinicians have always been intrigued by the observation that psoriatic affection of the mucosa, if at all existing, is only seen as very rare events in the lips and tongue sparing buccopharyngeal sites. This prompted us to establish an experimental model system comparing psoriatic-involved skin and peritonsillar mucosa from tonsillectomies by a reverse transcriptase-polymerase chain reaction/differential display strategy. Among more than 60 cDNA species to be displayed in psoriasis, but missing in peritonsillar mucosa, one species was identified as coding for the RNA polymerase IIA seventh subunit (hsRPB7 gene) as a most critical factor for DNA to RNA transcription. Immunohistochemistry showed a hitherto unknown, distinctive pattern of hsRPB7 expression that was 1) tissue type-dependent with a surplus in skin keratinocytes and a near absence in peritonsillar mucosa, 2) tightly regulated by the keratinocyte differentiation process with a sharp suprabasal up-regulation in contrast to a basal down-regulation, and 3) substantially augmented in psoriatic-involved skin as compared to normal and psoriatic uninvolved skin. Keratinocytes of actinic keratoses also showed a strong hsRPB7 expression that however did not strictly spare the basal cell layer presumably reflecting the disturbed intraepidermal stratification because of the premalignant status of these precancerous lesions.
Böckelmann
R
R
Department of Dermatology and Venereology, Otto-von-Guericke-University, Magdeburg, Germany.
Neugebauer
P
P
Paseban
N D
ND
Hüttemann
M
M
Gollnick
H
H
Bonnekoh
B
B
D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004817:Epidermis / Q000201:enzymology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000201:enzymology* / Q000473:pathology; D014066:Palatine Tonsil / Q000201:enzymology / Q000473:pathology; D011565:Psoriasis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D012313:RNA; D012319:RNA Polymerase II