Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2

Area of Science:

• Dermatology
• Cell Biology
• Biophysics

Background:

• Aberrant mechanotransduction and compromised epithelial barrier function are implicated in inflammatory skin disorders.
• The precise cytoskeletal mechanisms governing epidermal inflammatory responses remain unclear.

Purpose of the Study:

• To investigate the cytoskeletal mechanisms regulating inflammatory responses in the epidermis.
• To elucidate the role of the Rho-myosin II pathway and adherens junctions in inflammation-induced keratinocyte changes.

Main Methods:

• Induction of a psoriatic phenotype in human keratinocytes and reconstructed human epidermis via cytokine stimulation.
• Analysis of Rho-myosin II pathway, adherens junction stability, and YAP nuclear entry.
• Pharmacological inhibition of ROCK2 using KD025.

Main Results:

• Inflammation upregulates the Rho-myosin II pathway and destabilizes adherens junctions (AJs), promoting YAP nuclear entry.
• Adherens junction integrity, not myosin II contractility, dictates YAP regulation in keratinocytes.
• ROCK2 regulates inflammation-induced AJ disruption, paracellular permeability, and YAP translocation independently of myosin II activation.

Conclusions:

• ROCK2 plays a critical role in shaping epidermal inflammatory responses through cytoskeletal and transcription-dependent mechanisms.
• Targeting ROCK2 may offer a therapeutic strategy for inflammatory skin disorders by restoring epithelial barrier function.