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Scientific article
Open access
English

Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2

Published iniScience, vol. 26, no. 3, 106195
Publication date2023-03-17
First online date2023-02-14
Abstract

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 contractilityper seis 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.

eng
Keywords
  • Biological sciences
  • Genomics
  • Immune response
  • Immunology
Citation (ISO format)
SHUTOVA, Maria et al. Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2. In: iScience, 2023, vol. 26, n° 3, p. 106195. doi: 10.1016/j.isci.2023.106195
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ISSN of the journal2589-0042
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