Apremilast prevents blistering in human epidermis by stabilization of keratinocyte adhesion in pemphigus
Nature Communications(2022)
摘要
Pemphigus vulgaris (PV) is a life-threatening blistering skin disease caused by autoantibodies (PV-IgG) destabilizing desmosomal adhesion. Current therapies focus on suppression of autoantibody formation and thus treatments directly stabilizing keratinocyte adhesion would fulfill an unmet medical need. We here demonstrate that apremilast, a phosphodiesterase 4 inhibitor used e.g. in psoriasis, prevents blistering in PV. Apremilast abrogated PV-IgG-induced loss of keratinocyte cohesion in ex-vivo epidermis and in vitro . This was paralleled by inhibition of keratin retraction and desmosome splitting but affected neither desmoglein (Dsg) depletion nor Dsg3 binding properties.
Apremilast induced phosphorylation of plakoglobin at serine 665 – a mechanisms which is known to stabilize cardiomyocyte cohesion. Interestingly, keratinocytes phospho-deficient at this side showed altered organization of Dsg1, Dsg3 and keratin filaments and impaired adhesion, which was not rescued by apremilast. These data identified a new mechanism of desmosome regulation and propose that apremilast is protective in pemphigus by stabilizing keratinocyte cohesion.
### Competing Interest Statement
The authors have declared no competing interest.
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