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Citations to this article

Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering
Volker Spindler, … , Enno Schmidt, Jens Waschke
Volker Spindler, … , Enno Schmidt, Jens Waschke
Published January 9, 2013
Citation Information: J Clin Invest. 2013;123(2):800-811. https://doi.org/10.1172/JCI60139.
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Research Article Dermatology Article has an altmetric score of 15

Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering

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Abstract

In pemphigus vulgaris, a life-threatening autoimmune skin disease, epidermal blisters are caused by autoantibodies primarily targeting desmosomal cadherins desmoglein 3 (DSG3) and DSG1, leading to loss of keratinocyte cohesion. Due to limited insights into disease pathogenesis, current therapy relies primarily on nonspecific long-term immunosuppression. Both direct inhibition of DSG transinteraction and altered intracellular signaling by p38 MAPK likely contribute to the loss of cell adhesion. Here, we applied a tandem peptide (TP) consisting of 2 connected peptide sequences targeting the DSG adhesive interface that was capable of blocking autoantibody-mediated direct interference of DSG3 transinteraction, as revealed by atomic force microscopy and optical trapping. Importantly, TP abrogated autoantibody-mediated skin blistering in mice and was effective when applied topically. Mechanistically, TP inhibited both autoantibody-induced p38 MAPK activation and its association with DSG3, abrogated p38 MAPK-induced keratin filament retraction, and promoted desmosomal DSG3 oligomerization. These data indicate that p38 MAPK links autoantibody-mediated inhibition of DSG3 binding to skin blistering. By limiting loss of DSG3 transinteraction, p38 MAPK activation, and keratin filament retraction, which are hallmarks of pemphigus pathogenesis, TP may serve as a promising treatment option.

Authors

Volker Spindler, Vera Rötzer, Carina Dehner, Bettina Kempf, Martin Gliem, Mariya Radeva, Eva Hartlieb, Gregory S. Harms, Enno Schmidt, Jens Waschke

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 Total
Citations: 2 2 3 6 2 4 5 7 6 2 4 8 2 53
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Citations to this article (53)

Title and authors Publication Year
The impact of signaling pathways on the desmosome ultrastructure in pemphigus
Schmitt T, Huber J, Pircher J, Schmidt E, Waschke J
Frontiers in Immunology 2025
Meeting report – Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases
Waschke J, Amagai M, Becker C, Delmar M, Duru F, Garrod DR, Gerull B, Green KJ, Hertl M, Kowalczyk AP, Niessen CM, Nusrat A, Schinner C, Schlegel N, Sivasankar S, Vielmuth F, Spindler V
Journal of Cell Science 2025
Role of auto-antibodies in the mechanisms of dengue pathogenesis and its progression: a comprehensive review.
Ghorai T, Sarkar A, Roy A, Bhowmick B, Nayak D, Das S
Archives of Microbiology 2024
Adhesion of pancreatic tumor cell clusters by desmosomal molecules enhances early liver metastases formation.
Dietrich N, Castellanos-Martinez R, Kemmling J, Heuser A, Schnoor M, Schinner C, Spindler V
Scientific Reports 2024
Apremilast prevents blistering in human epidermis and stabilizes keratinocyte adhesion in pemphigus.
Sigmund AM, Winkler M, Engelmayer S, Kugelmann D, Egu DT, Steinert LS, Fuchs M, Hiermair M, Radeva MY, Bayerbach FC, Butz E, Kotschi S, Hudemann C, Hertl M, Yeruva S, Schmidt E, Yazdi AS, Ghoreschi K, Vielmuth F, Waschke J
Nature Communications 2023
Dsg3 epitope-specific signalling in pemphigus
Schmitt T, Hudemann C, Moztarzadeh S, Hertl M, Tikkanen R, Waschke J
Frontiers in immunology 2023
Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions
Emtenani S, Hertl M, Schmidt E, Hudemann C
Frontiers in immunology 2023
Desmosomal Cadherins in Health and Disease
M Hegazy, A Perl, S Svoboda, K Green
Annual review of pathology 2022
Desmoglein 2 can undergo Ca2+-dependent interactions with both desmosomal and classical cadherins including E-cadherin and N-cadherin
M Fuchs, D Kugelmann, N Schlegel, F Vielmuth, J Waschke
Biophysical Journal 2022
Mechanisms Causing Acantholysis in Pemphigus-Lessons from Human Skin
Egu DT, Schmitt T, Waschke J
Frontiers in immunology 2022
Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases
Ujiie H, Rosmarin D, Schön MP, Ständer S, Boch K, Metz M, Maurer M, Thaci D, Schmidt E, Cole C, Amber KT, Didona D, Hertl M, Recke A, Graßhoff H, Hackel A, Schumann A, Riemekasten G, Bieber K, Sprow G, Dan J, Zillikens D, Sezin T, Christiano AM, Wolk K, Sabat R, Kridin K, Werth VP, Ludwig RJ
Frontiers in Medicine 2022
Role of ADAM10 and ADAM17 in the Regulation of Keratinocyte Adhesion in Pemphigus Vulgaris
Kugelmann D, Anders M, Sigmund AM, Egu DT, Eichkorn RA, Yazdi AS, Sárdy M, Hertl M, Didona D, Hashimoto T, Waschke J
Frontiers in immunology 2022
Structure and regulation of desmosomes in intercalated discs: Lessons from epithelia
Yeruva S, Waschke J
Journal of Anatomy 2022
Autoantibody-Specific Signalling in Pemphigus
T Schmitt, J Waschke
Frontiers in Medicine 2021
Cadherin Signaling in Cancer and Autoimmune Diseases
M Sisto, D Ribatti, S Lisi
International journal of molecular sciences 2021
Stabilization of desmoglein-2 binding rescues arrhythmia in arrhythmogenic cardiomyopathy
Camilla Schinner, Bernd Markus Erber, Sunil Yeruva, Angela Schlipp, Vera Rötzer, Ellen Kempf, Sebastian Kant, Rudolf Leube, Thomas D. Mueller, Jens Waschke
JCI Insight 2020
Cardiomyocyte adhesion and hyper-adhesion differentially require ERK1/2 and plakoglobin.
Maria Shoykhet, Sebastian Trenz, Ellen Kempf, Tatjana Williams, Brenda Gerull, Camilla Schinner, Sunil Yeruva, Jens Waschke
JCI Insight 2020
Identification of novel therapeutic targets for blocking acantholysis in pemphigus
IA Burmester, S Flaswinkel, CS Thies, A Kasprick, M Kamaguchi, V BumillerBini, S Emtenani, N Feldmann, K Kridin, E Schmidt, N Beek, D Zillikens, CM Hammers, JE Hundt, RJ Ludwig
British Journal of Pharmacology 2020
The inotropic agent digitoxin strengthens desmosomal adhesion in cardiac myocytes in an ERK1/2-dependent manner
C Schinner, S Olivares-Florez, A Schlipp, S Trenz, M Feinendegen, H Flaswinkel, E Kempf, DT Egu, S Yeruva, J Waschke
Basic Research in Cardiology 2020
Current Clinical Trials in Pemphigus and Pemphigoid
K Izumi, K Bieber, RJ Ludwig
Frontiers in immunology 2019
Role of Dsg1- and Dsg3-Mediated Signaling in Pemphigus Autoantibody-Induced Loss of Keratinocyte Cohesion
E Walter, F Vielmuth, MT Wanuske, M Seifert, R Pollmann, R Eming, J Waschke
Frontiers in immunology 2019
Role of Src and Cortactin in Pemphigus Skin Blistering
D Kugelmann, V Rötzer, E Walter, DT Egu, MT Fuchs, F Vielmuth, H Vargas-Robles, M Schnoor, M Hertl, R Eming, K Rottner, A Schmidt, V Spindler, J Waschke
Frontiers in immunology 2019
Plakophilin 1 but not plakophilin 3 regulates desmoglein clustering
M Fuchs, M Foresti, MY Radeva, D Kugelmann, R Keil, M Hatzfeld, V Spindler, J Waschke, F Vielmuth
Cellular and Molecular Life Sciences 2019
Aktuelle Therapie des Pemphigus
N van Beek, D Zillikens, E Schmidt
Der Hautarzt 2019
Pemphigus: a Comprehensive Review on Pathogenesis, Clinical Presentation and Novel Therapeutic Approaches
R Pollmann, T Schmidt, R Eming, M Hertl
Clinical Reviews in Allergy & Immunology 2018
Atomic Force Microscopy Provides New Mechanistic Insights into the Pathogenesis of Pemphigus
F Vielmuth, V Spindler, J Waschke
Frontiers in immunology 2018
Keratins Regulate p38MAPK-Dependent Desmoglein Binding Properties in Pemphigus
F Vielmuth, E Walter, M Fuchs, MY Radeva, F Buechau, TM Magin, V Spindler, J Waschke
Frontiers in immunology 2018
Keratin Retraction and Desmoglein3 Internalization Independently Contribute to Autoantibody-Induced Cell Dissociation in Pemphigus Vulgaris
E Schlögl, MY Radeva, F Vielmuth, C Schinner, J Waschke, V Spindler
Frontiers in immunology 2018
Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model
T Sajda, AA Sinha
Frontiers in immunology 2018
Pemphigus—A Disease of Desmosome Dysfunction Caused by Multiple Mechanisms
V Spindler, J Waschke
Frontiers in immunology 2018
Immunoadsorption of Desmoglein-3-Specific IgG Abolishes the Blister-Inducing Capacity of Pemphigus Vulgaris IgG in Neonatal Mice
M Hofrichter, J Dworschak, S Emtenani, J Langenhan, F Weiß, L Komorowski, D Zillikens, W Stöcker, C Probst, E Schmidt, S Goletz
Frontiers in immunology 2018
Setting the target for pemphigus vulgaris therapy
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Mechanisms of Autoantibody-Induced Pathology
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Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration
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European Journal of Immunology 2017
Different signaling patterns contribute to loss of keratinocyte cohesion dependent on autoantibody profile in pemphigus
E Walter, F Vielmuth, L Rotkopf, M Sárdy, ON Horváth, M Goebeler, E Schmidt, R Eming, M Hertl, V Spindler, J Waschke
Scientific Reports 2017
Crosstalk between Signaling Pathways in Pemphigus: A Role for Endoplasmic Reticulum Stress in p38 Mitogen-Activated Protein Kinase Activation?
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Meibomian gland cells display a differentiation-dependent composition of desmosomes
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Loss of Desmoglein Binding Is Not Sufficient for Keratinocyte Dissociation in Pemphigus
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E-cadherin and Src associate with extradesmosomal Dsg3 and modulate desmosome assembly and adhesion
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