Gene Involved in Defective Skin Barrier and Eczema and Ichthyosis Identified Interview with:

Akio Kihara, PhD. Laboratory of Biochemistry Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan

Dr. Akio Kihara

Akio Kihara, PhD.
Laboratory of Biochemistry
Faculty of Pharmaceutical Sciences, Hokkaido University
Sapporo, Japan What is the background for this study? What are the main findings?

Response: The skin barrier is the most powerful defensive mechanism terrestrial animals possess against pathogens and harmful substances such as allergens and pollutants. Recent studies indicate that lipids play a central role in skin barrier formation. Multi-lamellar structures consisting of lipids are formed extracellularly in the stratum corneum, the outermost layer of epidermis, and their high hydrophobicity prevents the invasion of external pathogens and compounds.

The stratum corneum-specific lipid acylceramide is especially important for skin barrier formation. Decreases in acylceramide levels are associated with cutaneous disorders such as ichthyosis and atopic dermatitis. However, the mechanism behind acylceramide production is poorly understood, especially regarding the last step of acylceramide production: i.e., esterification of ω-hydroxyceramide with linoleic acid. This means that the broader picture of the molecular mechanisms behind skin barrier formation still remained unclear.

Although PNPLA1 has been identified as an ichthyosis-causative gene, its function in skin barrier formation remains unresolved. In the present study, we revealed that PNPLA1 catalyzes the last step of acylceramide synthesis. Our finding completes our knowledge of the entire pathway of the acylceramide production, providing important insights into the molecular mechanisms of skin barrier formation. What should readers take away from your report?

Response: Skin barrier protects us from pathogens, allergens and other harmful substances. Therefore, defects of the skin barrier cause several skin diseases such as atopic dermatitis and ichthyosis. The stratum corneum-specific lipid acylceramide plays a pivotal role in forming this barrier. There is no curative treatment for atopic dermatitis, patients are currently given only symptomatic therapies. No treatment has been established for ichthyosis. Therefore, it is essential to restore the functions of the skin barrier to treat such patients. What recommendations do you have for future research as a result of this study?

Response: Development of new therapeutic medicines that increase acylceramide synthesis and therefore restore the skin barrier is needed for treatment of atopic dermatitis and ichthyosis.

No disclosures Thank you for your contribution to the community.


Nat Commun. 2017 Mar 1;8:14610. doi: 10.1038/ncomms14610.
PNPLA1 is a transacylase essential for the generation of the skin barrier lipid ω-O-acylceramide.
Ohno Y1, Kamiyama N1, Nakamichi S1, Kihara A1.

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Last Updated on April 18, 2017 by Marie Benz MD FAAD