| Title: | Wnt/beta-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes |
| Authors: | Kosumi, Hideyuki Browse this author |
| Watanabe, Mika Browse this author |
| Shinkuma, Satoru Browse this author |
| Nohara, Takuma Browse this author |
| Fujimura, Yu Browse this author |
| Tsukiyama, Tadasuke Browse this author →KAKEN DB |
| Donati, Giacomo Browse this author |
| Iwata, Hiroaki Browse this author →KAKEN DB |
| Nakamura, Hideki Browse this author |
| Ujiie, Hideyuki Browse this author →KAKEN DB |
| Natsuga, Ken Browse this author →KAKEN DB |
| Issue Date: | Jun-2022 |
| Publisher: | Elsevier |
| Journal Title: | Journal of investigative dermatology |
| Volume: | 142 |
| Issue: | 6 |
| Start Page: | 1576 |
| End Page: | 1586 e2 |
| Publisher DOI: | 10.1016/j.jid.2021.10.018 |
| Abstract: | 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/0-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/beta-catenin signaling in HD assembly. Atypical protein kinase C inhibition ameliorated the phenotypes of Wnt-inhibited cells. These findings show that Wnt/beta-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. |
| Rights: | © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/89791 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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