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Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2

Aberrant mechanotransduction and compromised epithelial barrier function are associated with numerous human pathologies including inflammatory skin disorders. However, the cytoskeletal mechanisms regulating inflammatory responses in the epidermis are not well understood. Here we addressed this quest...

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Autores principales: Shutova, Maria S., Borowczyk, Julia, Russo, Barbara, Sellami, Sihem, Drukala, Justyna, Wolnicki, Michal, Brembilla, Nicolo C., Kaya, Gurkan, Ivanov, Andrei I., Boehncke, Wolf-Henning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986521/
https://www.ncbi.nlm.nih.gov/pubmed/36890793
http://dx.doi.org/10.1016/j.isci.2023.106195
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author Shutova, Maria S.
Borowczyk, Julia
Russo, Barbara
Sellami, Sihem
Drukala, Justyna
Wolnicki, Michal
Brembilla, Nicolo C.
Kaya, Gurkan
Ivanov, Andrei I.
Boehncke, Wolf-Henning
author_facet Shutova, Maria S.
Borowczyk, Julia
Russo, Barbara
Sellami, Sihem
Drukala, Justyna
Wolnicki, Michal
Brembilla, Nicolo C.
Kaya, Gurkan
Ivanov, Andrei I.
Boehncke, Wolf-Henning
author_sort Shutova, Maria S.
collection PubMed
description Aberrant mechanotransduction and compromised epithelial barrier function are associated with numerous human pathologies including inflammatory skin disorders. However, the cytoskeletal mechanisms regulating inflammatory responses in the epidermis are not well understood. Here we addressed this question by inducing a psoriatic phenotype in human keratinocytes and reconstructed human epidermis using a cytokine stimulation model. We show that the inflammation upregulates the Rho-myosin II pathway and destabilizes adherens junctions (AJs) promoting YAP nuclear entry. The integrity of cell-cell adhesion but not the myosin II contractility per se is the determinative factor for the YAP regulation in epidermal keratinocytes. The inflammation-induced disruption of AJs, increased paracellular permeability, and YAP nuclear translocation are regulated by ROCK2, independently from myosin II activation. Using a specific inhibitor KD025, we show that ROCK2 executes its effects via cytoskeletal and transcription-dependent mechanisms to shape the inflammatory response in the epidermis.
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spelling pubmed-99865212023-03-07 Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2 Shutova, Maria S. Borowczyk, Julia Russo, Barbara Sellami, Sihem Drukala, Justyna Wolnicki, Michal Brembilla, Nicolo C. Kaya, Gurkan Ivanov, Andrei I. Boehncke, Wolf-Henning iScience Article Aberrant mechanotransduction and compromised epithelial barrier function are associated with numerous human pathologies including inflammatory skin disorders. However, the cytoskeletal mechanisms regulating inflammatory responses in the epidermis are not well understood. Here we addressed this question by inducing a psoriatic phenotype in human keratinocytes and reconstructed human epidermis using a cytokine stimulation model. We show that the inflammation upregulates the Rho-myosin II pathway and destabilizes adherens junctions (AJs) promoting YAP nuclear entry. The integrity of cell-cell adhesion but not the myosin II contractility per se is the determinative factor for the YAP regulation in epidermal keratinocytes. The inflammation-induced disruption of AJs, increased paracellular permeability, and YAP nuclear translocation are regulated by ROCK2, independently from myosin II activation. Using a specific inhibitor KD025, we show that ROCK2 executes its effects via cytoskeletal and transcription-dependent mechanisms to shape the inflammatory response in the epidermis. Elsevier 2023-02-14 /pmc/articles/PMC9986521/ /pubmed/36890793 http://dx.doi.org/10.1016/j.isci.2023.106195 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shutova, Maria S.
Borowczyk, Julia
Russo, Barbara
Sellami, Sihem
Drukala, Justyna
Wolnicki, Michal
Brembilla, Nicolo C.
Kaya, Gurkan
Ivanov, Andrei I.
Boehncke, Wolf-Henning
Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2
title Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2
title_full Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2
title_fullStr Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2
title_full_unstemmed Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2
title_short Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2
title_sort inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via rock2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986521/
https://www.ncbi.nlm.nih.gov/pubmed/36890793
http://dx.doi.org/10.1016/j.isci.2023.106195
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