Reduced hydration-induced decreased caveolin-1 expression causes epithelial-to-mesenchymal transition.

The reduced hydration environment induced by disruption of epithelial barrier function after injury results in excessive scarring, but the underlying mechanisms are poorly understood. We demonstrated that exposing keratinocytes to a reduced hydration environment causes epithelial-to-mesenchymal transition (EMT) and induces caveolin-1-dependent downregulation of E-cadherin. Reduced caveolin-1 expression and increased Snail expression are associated with low expression levels of E-cadherin. Caveolin-1 downregulation increases the transcriptional activity of β-catenin-TCF/LEF-1, and overexpression of caveolin-1 inhibits EMT that results from reduced hydration. Our findings suggest a role for caveolin-1 downregulation in linking aberrant EMT to the reduced hydration environment: findings that may lead to new developments in the prevention and treatment of hypertrophic scar.