Alterations in the desquamation-related proteolytic cleavage of corneodesmosin and other corneodesmosomal proteins in psoriatic lesional epidermis.
BACKGROUND
Desquamation occurs after proteolysis of corneodesmosomal proteins, including corneodesmosin (CDSN), by proteases of the kallikrein family, particularly KLK7. Impaired desquamation is one of the features of psoriasis, and psoriasis-associated single nucleotide polymorphisms of the CDSN gene may potentially modify the proteolysis of the encoded protein.


OBJECTIVE
To test whether the proteolysis of CDSN and other corneodesmosomal components is altered in psoriatic epidermis.


METHODS
Total protein extracts obtained by tape-stripping of nonlesional and lesional skin from 11 patients were compared by immunoblotting experiments.


RESULTS
An almost intact form of CDSN that has never been observed previously in the normal upper stratum corneum was detected in the lesional skin extracts, showing an altered proteolytic processing of the protein. This form was also observed in the nonlesional skin extracts, but in lower amounts. For most patients, increased amounts of desmoglein 1, plakoglobin and of high molecular weight fragments of desmocollin 1 were detected in the lesional skin. For most of them, similar amounts of KLK7 were immunodetected in both nonlesional and lesional skin extracts. No particular differences were observed related to the psoriasis type, the HLA-Cw6 status of the patients or any particular CDSN polymorphisms.


CONCLUSIONS
We detected a near full-length form of CDSN that has not been previously observed in normal stratum corneum. The results suggest a reduced degradation of all corneodesmosomal proteins in psoriatic lesions which probably reflects the persistence of corneodesmosomes.
Simon
M
M
University of Toulouse III-CNRS UMR5165, Institut Fédératif de Recherche Claude de Préval, IFR30 (INSERM-CNRS-Université Paul Sabatier-Centre Hospitalier Universitaire de Toulouse), 31059 Toulouse, France. msimon@udear.cnrs.fr
Tazi-Ahnini
R
R
Jonca
N
N
Caubet
C
C
Cork
M J
MJ
Serre
G
G
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D051183:Desmoglein 1 / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism*
C109656:CDSN protein, human; D051183:Desmoglein 1; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007610:Kallikreins