Expression of Epithelial-Mesenchymal Transition Markers in Epidermal Layer of Atopic Dermatitis.

ABSTRACT

The epithelial-mesenchymal transition (EMT) is a phenomenon, in which epithelial cells acquire a mesenchymal cell phenotype. It is important during wound healing; however, chronic inflammation leads to excessive EMT and causes tissue barrier dysfunction with hyperplasia. EMT is induced by several cytokines, such as interleukin (IL)-4 and IL-13. Additionally, IL-4 and IL-13 are known to increase in atopic dermatitis (AD) characterized by intense itching and eczema. Therefore, we assumed that there was commonality between the respective EMT and AD phenotypes. Herein, we evaluated EMT marker expression in AD skin and demonstrated that EMT-maker Snai1 and Twist expression were increased in AD mice model and patients with AD. Moreover, the epithelial-marker keratin 5 and mesenchymal marker Vimentin were co-expressed in the skin epidermis of mice with AD, suggesting the existence of hybrid epithelial-mesenchymal (E/M) cells possessing both epithelial and mesenchymal characteristics. In fact, we found that ΔNp63a, a stabilizing factor for hybrid E/M cells, was upregulated in the skin epidermis of the AD model mouse. Interestingly, increased expression of EMT markers was observed even at a nonlesion site in a patient with AD without initial inflammation or scratching. Therefore, EMT-like phenomena may occur independently of wound healing in skin of patients with AD.