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Wnt/β-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes

Published:November 02, 2021DOI:https://doi.org/10.1016/j.jid.2021.10.018
      Hemidesmosomes (HDs) are adhesion complexes that promote epithelial–stromal attachment in stratified and complex epithelia, including the epidermis. In various biological processes, such as differentiation and migration of epidermal keratinocytes during wound healing or carcinoma invasion, quick assembly and disassembly of HDs are prerequisites. In this study, we show that inhibition of Wnt/β-catenin signaling disturbs HD organization in keratinocytes. Screening with inhibitors identified the depletion of HD components and HD-like structures through Wnt inhibition, but keratinocyte differentiation was not affected. Wnt inhibition significantly diminished plectin and type XVII collagen expression in the basal side of Wnt-inhibited cells and the dermo–epidermal junction of the Wnt-inactive murine basal epidermis. Similar to Wnt inhibition, PLEC-knockout cells or cells with plectin–type XVII collagen binding defects showed type XVII collagen reduction in the basal side of the cells, implying the possible involvement of Wnt/β-catenin signaling in HD assembly. Atypical protein kinase C inhibition ameliorated the phenotypes of Wnt-inhibited cells. These findings show that Wnt/β-catenin signaling regulates the localization of HD components in keratinocytes and that the atypical protein kinase C pathway is involved in Wnt inhibition‒induced HD disarrangement. Our study suggests that the Wnt signaling pathway could be a potential therapeutic target for treating HD-defective diseases, such as epidermolysis bullosa.

      Abbreviations:

      aPKC (atypical protein kinase C), COL17 (type XVII collagen), DEJ (dermo‒epidermal junction), EB (epidermolysis bullosa), HD (hemidesmosome), IF (immunofluorescence), KC (keratinocyte), KO (knockout), NHEK (normal human epidermal keratinocyte), PCN (plectin), PKC (protein kinase C)
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