Evidence map›Paper›PMID 41037786›Full record

ArticleJCI insight2025

SERPINB5/TGF-β signaling modulates desmoplakin membrane localization and ameliorates pemphigus vulgaris skin blistering.

Maitreyi Rathod, Mariam Petrosyan, Aude Zimmermann, Maike Märker, Tobias Gosau, Henriette Franz, Tomás Cunha, Dario Didona, Michael Hertl, Enno Schmidt and 1 more

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Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Maitreyi RathodInstitute of Anatomy and Experimental Morphology, University Medical Centre-Eppendorf, Hamburg, Germany.
Mariam PetrosyanInstitute of Anatomy and Experimental Morphology, University Medical Centre-Eppendorf, Hamburg, Germany.
Aude ZimmermannDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Maike MärkerInstitute of Anatomy and Experimental Morphology, University Medical Centre-Eppendorf, Hamburg, Germany.
Tobias GosauInstitute of Anatomy and Experimental Morphology, University Medical Centre-Eppendorf, Hamburg, Germany.
Henriette FranzDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Tomás CunhaDepartment of Dermatology and Allergology, Philipps-University Marburg, Marburg, Germany.
Dario DidonaDepartment of Dermatology and Allergology, Philipps-University Marburg, Marburg, Germany.
Michael HertlDepartment of Dermatology and Allergology, Philipps-University Marburg, Marburg, Germany.
Enno SchmidtLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Volker SpindlerInstitute of Anatomy and Experimental Morphology, University Medical Centre-Eppendorf, Hamburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Impairment of desmosomal cell-cell adhesion leads to life-threatening diseases, such as the autoimmune skin-blistering disorder pemphigus vulgaris (PV). Disease management strategies that stabilize intercellular adhesion, in addition to the existing immunosuppression therapies, may result in improved clinical outcomes. Previous findings showed that the serine protease inhibitor SERPINB5 promotes intercellular adhesion by binding to and regulating the localization of the desmosomal adapter molecule desmoplakin (DSP) at the plasma membrane. We here show that SERPINB5 overexpression prevents PV-IgG-mediated loss of cell-cell adhesion and DSP dissociation from the cell membrane. We mechanistically demonstrate that SERPINB5 loss deregulates TGF-β signaling, a pathway known to destabilize DSP in keratinocytes. TGF-β signaling was also activated in skin biopsies of patients with PV and keratinocytes treated with PV autoantibodies, suggesting a contribution to disease. Inhibition of TGF-β signaling ameliorated PV-IgG-mediated loss of cell-cell adhesion, increased DSP membrane expression, and prevented PV-IgG-induced blister formation in a human ex vivo skin model. Together, SERPINB5 modulates DSP and intercellular adhesion through the regulation of TGF-β signaling. Further, TGF-β signaling was identified as a potential target for pemphigus treatment.

Indexed as

DesmoplakinsDesmosomesPemphigusSerpinsTransforming Growth Factor betaAgedAged, 80 and overBiopsyCell AdhesionCell MembraneFemaleHaCaT CellsHumansImmunoglobulin GKeratinocytesMaleDesmoplakinsImmunoglobulin GSERPIN-B5SerpinsTransforming Growth Factor betaCell biologyCell migration/adhesionDermatologySignal transductionSkin

Identifiers

PMID41037786
PMCPMC12643518

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.