LB894 Psoriatic 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 involved molecular mechanisms not well understood. We investigated alterations in cell-cell adhesions, mechanosensitive effector molecules mechanosignaling epidermis during inflammation using psoriasis as a model disease. Psoriatic phenotype keratinocytes reconstructed was induced cytokine stimulation (“M5” cocktail comprising of IL-17A, IL-22, Oncostatin M, TNFa, IL-1a). show that upregulates Rho-myosin II pathway destabilizes adherens junctions promoting YAP nuclear entry. integrity adhesion but myosin contractility per se is determinative factor for regulation epidermal keratinocytes. The inflammation-induced disruption junctions, increased paracellular permeability translocation regulated by ROCK2, independently from activation. Using specific inhibitor KD025, we ROCK2 executes its effects via cytoskeletal transcription-dependent to shape response epidermis. inhibition, therefore, may be promising strategy topical treatment cutaneous general particular.