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Endogenous Retroviral-Like Aspartic Protease, SASPase as a Key Modulator of Skin Moisturization

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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.

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Acknowledgments

I thank Itsumi Ohmori and Sayaka Katahira-Tayama for their technical assistance. I thank Keiko Mizuno and Kaoru Orihashi for critical reading of the manuscript. I thank Drs. Masayuki Amagai, Akiharu Kubo, Jun Kudoh and Kenichi Miyamoto (Keio University) and Dr. Johji Inazawa (Tokyo Medical and Dental University) for supporting this project and Mr. Yoshihiko Tsuda (Davinci Medical Illustration Office) for illustration of figures. I also thank KAN Research Insitute Inc. for provising materials. This work was supported by a Grant-in-Aid for Scientific Research to Takeshi Matsui, “Program for Improvement of Research Environment for Young Researchers” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan to Takeshi Matsui, research grants from the Nakatomi Foundation, the Cosmetology Research Foundation, and the Naito Foundation to Takeshi Matsui, and Health and Labour Sciences Research Grants for Research on Allergic Diseases and Immunology from the Ministry of Health, Labour, and Welfare.

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  1. Hiiragi Laboratory, Institute for Integrated Cell – Material Sciences (iCeMS), Kyoto University, iCeMS Complex2, Yoshida-Honmachi, Sakyo-ku, Kyoto, 606-8501, Japan

    Takeshi Matsui Ph.D.

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  1. Eviderm Institute, Bergshamra Allé 9, Solna, 17077, Sweden

    Marie Lodén

  2. School of Medicine, Department Dermatology, University of California, San Francisco, Divisadero 1701, San Francisco, 94143-0989, California, USA

    Howard I. Maibach

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Matsui, T. (2012). Endogenous Retroviral-Like Aspartic Protease, SASPase as a Key Modulator of Skin Moisturization. In: Lodén, M., Maibach, H. (eds) Treatment of Dry Skin Syndrome. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27606-4_12

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