A research group led by Professor Akio Kihara of the Graduate School of Pharmaceutical Sciences, Hokkaido University succeeded in identifying a gene (PNPLA1) that remained unidentified until the end among the enzyme genes involved in acylceramide production, and succeeded in identifying the molecule that produces acylceramide. The whole picture of the mechanism was elucidated.

 The skin barrier acts like a breakwater for living organisms that blocks the invasion of pathogens and allergens.Therefore, abnormalities in the skin barrier cause skin diseases such as atopic dermatitis and ichthyosis.
Recent studies have revealed that the main body of the skin barrier is lipids, and among them, lipids called acylceramides are the most important.The existence of acylceramide has been known for more than 30 years, but it has not been clarified how it is produced in vivo.

 The research group of Professor Kihara and his colleagues has been working on the elucidation of the molecular mechanism of acylceramide production, and have succeeded in elucidating intermediates in the production pathway, elucidating the order of chemical reactions, and identifying related enzyme genes.However, the identification of the enzyme gene involved in the final step of acylceramide production remained unclear.Elucidating this was an important issue not only for elucidating the whole picture of acylceramide production, but also for elucidating the molecular mechanism of skin barrier formation.

 This time, the research group established a cultured cell line that produces omega hydroxide ultra-long chain ceramide, and evaluated the acylceramide production activity using these cells.As a result, we succeeded in identifying PNPLA1 as an enzyme gene that catalyzes the final step of acylceramide production. The PNPLA1 protein catalyzes the reaction of adding the fatty acid linoleic acid to omega hydroxide ceramide to produce acylceramide.The research group also revealed by biochemical methods that the source of this linoleic acid is triglyceride (neutral lipid in which three fatty acids are added to glycerol), and that the PNPLA3 protein is classified into an enzyme called transacylase. I made it.In addition, PNPLA1 was known as the causative gene of congenital ichthyosis, but this result also clarified the relationship between gene mutation and pathological condition.

 Atopic dermatitis still relies on symptomatic treatment, and there is no cure for ichthyosis.Restoration of the skin barrier that causes the disease is essential for the development of effective therapeutic agents for these skin diseases.
Now that the entire molecular mechanism of the production of acylceramide, which is the most important lipid for skin barrier formation, has been elucidated, it will be possible to search for compounds that enhance the production of acylceramide in the future, which is called skin barrier enhancement. The development of therapeutic agents for skin diseases by new measures is expected.

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Strong cooperation with industry and regions "Practical science unique to Hokkaido University" leads the world

The origin of Hokkaido University dates back to Sapporo Agricultural College, which was established in 1876.Throughout its long history, we have cultivated the basic principles of "frontier spirit," "cultivating internationality," "education for all," and "emphasis on practical studies."Based on this philosophy, he has a high level of academic background that is internationally accepted, and has accurate judgment and a leader […].

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