Desmoglein 3-Dependent Signaling Regulates Keratinocyte Migration and Wound Healing

The Journal of Investigative Dermatology
Vera RötzerJens Waschke

Abstract

The desmosomal transmembrane adhesion molecules desmoglein 3 (Dsg3) and desmocollin 3 (Dsc3) are required for strong keratinocyte cohesion. Recently, we have shown that Dsg3 associates with p38 mitogen-activated protein kinase (p38MAPK) and suppresses its activity. Here, we further investigated the role of Dsg3-dependent control of p38MAPK function. Dsg3-deficient mice display recurrent spontaneously healing skin erosions. In lesional and perilesional biopsies, p38MAPK activation was detectable compared with control animals. This led us to speculate that Dsg3 regulates wound repair in a p38MAPK-dependent manner. Indeed, scratch-wounded keratinocyte monolayers exhibited p38MAPK activation and loss of Dsg3 in cells lining the wound edge. Human keratinocytes after silencing of Dsg3 as well as primary cells isolated from Dsg3 knockout animals exhibited accelerated migration, which was further corroborated in an ex vivo skin outgrowth assay. Importantly, migration was efficiently blocked by inhibition of p38MAPK, indicating that p38MAPK mediates the effects observed upon loss of Dsg3. In line with this, we show that levels of active p38MAPK associated with Dsc3 are increased in Dsg3-deficient cells. These data indicate that Dsg3 con...Continue Reading

Citations

Aug 20, 2016·Histochemistry and Cell Biology·Vera RötzerJens Waschke
Jul 1, 2018·The Journal of Cell Biology·Chen Yuan KamKathleen J Green
May 7, 2020·Microbiome·Kenzie D BirseGrace Aldrovandi
Feb 17, 2018·Frontiers in Immunology·Volker Spindler, Jens Waschke
Mar 10, 2017·Molecular Carcinogenesis·Katharina HützVolker Spindler
Apr 5, 2018·Frontiers in Immunology·Franziska VielmuthJens Waschke
Apr 13, 2018·Frontiers in Immunology·Franziska VielmuthJens Waschke
Nov 17, 2020·Frontiers in Immunology·Anna M SigmundFranziska Vielmuth
Dec 24, 2020·Acta Physiologica·Marie-Therès WanuskeVolker Spindler
May 1, 2021·International Journal of Molecular Sciences·Iwona Ziółkowska-SuchanekNatalia Rozwadowska
Dec 12, 2018·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Jens Waschke
Aug 27, 2021·Frontiers in Medicine·Thomas Schmitt, Jens Waschke

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