TY  - JOUR
A1  - Hartlieb, Eva
A1  - Kempf, Bettina
A1  - Partilla, Miriam
A1  - Vigh, Balázs
A1  - Spindler, Volker
A1  - Waschke, Jens
T1  - Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion
JF  - PLoS ONE
N2  - Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.
KW  - expression
KW  - inhibition
KW  - DSG2
KW  - cell adhesion
KW  - desmosomal cadherins
KW  - pemphigus vulgaris
KW  - phenotype
KW  - mice
KW  - transinteraction
KW  - reorganization
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131192
VL  - 8
IS  - 1
ER  - 
TY  - THES
A1  - Kempf, Bettina
T1  - Interaktion ausgewählter Mechanismen der Pemphigus-Pathogenese
T1  - Interaction of selected mechanisms of the pathogenesis of pemphigus
N2  - Bei der Autoimmunerkrankung Pemphigus vulgaris führen Antikörper zur charakteristischen suprabasalen Akantholyse und Blasenbildung der Epidermis, indem sie an spezifische Antigene, Dsg3 (Desmoglein 3) und Dsg1 (Desmoglein 1), auf der Zelloberfläche der Keratinozyten binden. Die Art und Weise, wie die multiplen zellulären Pathomechanismen zusammenwirken und das potenziell tödliche Krankheitsbild hervorrufen, ist jedoch bislang noch weitgehend unklar. In der vorliegenden Arbeit wurden entscheidende, durch die Autoantikörper hervorgerufene, pathologische intrazelluläre Prozesse genauer untersucht und deren Stellenwert beleuchtet.
N2  - In the autoimmune disease Pemphigus autoantibodies lead to characteristic suprabasal acantholysis and blistering of the epidermis by binding to specific antigens, Dsg3 (desmoglein 3) and Dsg1 (desmoglein 1) on the surface of keratinocytes. The way, how multiple cellular pathomechanisms work together causing the potentially lethal clinical picture, is yet largely unknown. In this work, decisive pathologic intracellular processes, caused by the autoantibodies, were investigated more closely and their respective significance illuminated.
KW  - pemphigus
KW  - Pemphigus
KW  - Autoimmunerkrankung
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220480
ER  -