Endogenous retroviral-like aspartic protease, saspase as a key modulator of skin moisturization

Abstract

Approximately 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 surface skin epidermis into a keratinized stratified squamous epithelium to prevent water loss and to protect the body from sunlight. During the long history of this epithelial evolution, humans have evolved the epithelia to be more functional, baring the stratum corneum (SC) as the outermost layer, which acts as a barrier against the external environment. This layer is hydrated by endogenous substances to avoid desiccation; however, the mechanisms responsible for maintaining hydration of the SC remain unclear at the molecular level. We have recently generated skin-specific retroviral-like aspartic protease (SASPase)-deficient hairless mice. The reduced activity of this enzyme in these mice results in dry skin with the accumulation of incorrectly processed profilaggrin and a marked decrease of filaggrin production. Missense human mutations that affect the protease activity have been detected in both atopic dermatitis patients and normal individuals. In this chapter, these findings obtained from SASPase-deficient hairless mice will be summarized. Our results provide novel concepts to assist in determining the complex pathophysiology of atopic dry skin. This molecular mechanism should provide clues in revealing the role of the SC in terrestrial animals and how they have adapted to life on land during the evolution of mammals.