A possible role of catenin dyslocalization in pemphigus vulgaris pathogenesis.
BACKGROUND
Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of beta- and gamma-catenins in blistering diseases. The objective of this study was to evaluate the role of beta- and gamma-catenins in the pathogenesis of acantholysis in pemphigus vulgaris.


METHODS
beta- and gamma-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients.


RESULTS
Healthy skin and normal oral mucosa showed a strong beta- and gamma-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of gamma-catenin was detected in 28/30 cases, and in 19/30 cases of PV for beta-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for beta-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for gamma-catenin.


CONCLUSIONS
Abnormal distribution of gamma-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. gamma-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the beta-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.
Lo Muzio
L
L
Institute of Dental Sciences, University of Ancona, Ancona, Italy. lomuziol@tin.it
Pannone
G
G
Staibano
S
S
Mignogna
M D
MD
Rubini
C
C
Ruocco
E
E
De Rosa
G
G
Sciubba
J J
JJ
D000051:Acantholysis / Q000473:pathology; D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis*; D051180:Desmoplakins; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology*; D010392:Pemphigus / Q000473:pathology*; D012867:Skin / Q000737:chemistry / Q000473:pathology*; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin