Host: The Japanese Society of Toxicology
Name : The 47th Annual Meeting of the Japanese Society of Toxicology
Date : 2020 -
About 360 million years ago (the late Devonian period), the first terrestrial vertebrate, amphibian emerged from water and adapted to life on land. These animals evolved their skin epidermis into a keratinized stratified squamous epithelium to prevent water loss and as protection from sunlight. Stratum corneum (SC) is the uppermost dead cell layer of skin epidermis and provides these protective barrier function. Previously, we reported that mammalian skin-specific retroviral-like aspartic protease SASPase are the key regulator of SC moisturization. It cleaves profilaggrin to produce filaggrin monomer in the lower SC. As its optimum pH of SASPase protease activity is low pH, we hypothesized that lower SC has an acidic environment. To determine the pH distribution in the SC, we fused two fluorescent proteins, pH-sensitive Venus and insensitive mCherry and generated mice expressing the fusion protein from the uppermost stratum granulosum (SG1 cells). Confocal microscopic analysis revealed that SC has three distinct pH layers, lower-slightly acidic, middle highly acidic and upper-neutral SC layers, rather than gradual change over SC layers. SC pH imaging in various parts of the body confirmed that the lower-acid SC layer consistently exists in tail, foot pad, ear and back skin irrespective of their thickness and compactness of SC. These findings collectively indicate that SC indeed has an environment to activate SASPase protease. Thus, co-option (exaptation) of SASPase gene function was achieved not only the acquirement of SASPase gene but also the generation of acidic SC, result in moisturization of mammalian skin.
