Dose-Dependent Role Of Claudin-1 In Epidermal Differentiation And Inflammation Over Time.

Claudin-1, which is the main component of tight junctions in the epidermis, has a key role in epidermal barrier systems. However, although evidence has been accumulated that the down-regulation of claudin-1 contributes to skin diseases in humans, claudin-1 knock-out (KO) mice die within 1 day after birth due to dehydration. To understand the role of claudin-1 in skin diseases, we established an in vivo analysis system using 6 patterns of claudin-1 expression level in mice. In the primary cultured keratinocytes isolated from these mice, the epithelial barrier function correlated with expression levels of claudin-1. On the other hand, the newborn mice showed abnormal skin differentiation, in which the degree of abnormality correlated with expression levels of claudin-1. The abnormality in skin differentiation was greater in the infant stages, but it reduced to an almost normal level towards the adult stages. Although infiltrating macrophages and neutrophils were not detected at birth, infant and adult mice showed their infiltration in a similar age-dependent manner. Our findings suggest that claudin-1 plays a critical role in differentiation and inflammation age-dependently. The results obtained will be discussed with special reference to human diseases.