P120-Catenin Regulates Epidermal Inflammation in a Cadherin-Dependent Manner

This study investigates the role of p120-catenin (p120) in epidermal inflammation and its relationship with E-cadherin (E-cad), a protein crucial for skin barrier function. The researchers created a knock-in mouse model with a mutated E-cad (E-cadLL) that prevents its endocytosis and degradation. They found that in mice with p120 ablation, there was a significant reduction in E-cad levels, leading to perinatal lethality, hair loss, and severe epidermal inflammation. However, in p120 null mice expressing the E-cadLL mutant, E-cad levels remained near normal, and both lethality and inflammatory phenotype were rescued. Histological analysis showed that the E-cadLL mutant also prevented epidermal thickening and hair loss. Gene expression analysis revealed that IL-6 and MIP-3α were significantly upregulated in p120 null mice, but not in those expressing the E-cadLL mutant. These results suggest that p120's primary function is to regulate cadherin levels and that cadherins play a significant role in controlling epidermal inflammation.