Keio University

Elucidating the Cell Death Process of Epidermal Keratinocytes—Intracellular Acidification Is Crucial for Normal Stratum Corneum Formation

Publish: April 20, 2021
Public Relations Office

April 20, 2021

RIKEN

Keio University School of Medicine

National Institute for Physiological Sciences, National Institutes of Natural Sciences

Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences

Japan Agency for Medical Research and Development

A joint research group—led by Deputy Team Leader Takeshi Matsui (at the time of the research), Visiting Scientist Nanako Kuzuwa (at the time of the research), and Team Leader Masayuki Amagai (Professor, Department of Dermatology, Keio University School of Medicine) of the Laboratory for Skin Homeostasis at the RIKEN Center for Integrative Medical Sciences—has clarified the process of cell death in epidermal keratinocytes and proposed a new form of cell death called "Corneoptosis."

These research findings are expected to help elucidate the pathogenesis of allergic diseases such as atopic dermatitis, which are known to involve barrier dysfunction of the stratum corneum on the skin's surface.

In the skin's epidermis, the stratum corneum (the outermost layer of the epidermis) is formed from the remaining cell bodies after organelles essential for cell survival, such as the nucleus and mitochondria, disappear (cell death). However, the mechanism by which the nucleus and mitochondria disappear has remained unclear.

The joint research group developed a proprietary live imaging method to observe the epidermis of living mice. They found that during the cell death process of granular layer cells, located beneath the stratum corneum, the intracellular calcium ion (Ca 2+ ) concentration increases for about one hour, after which the cell interior acidifies while the Ca 2+ concentration remains high. Without this acidification, the nucleus fails to disappear, preventing the formation of normal corneocytes. The group also revealed that the timing of this acidification is regulated by the thermosensitive calcium channel protein TRPV3.

This research will be published in the online edition of the scientific journal "Proceedings of the National Academy of Sciences of the United States of America" (PNAS) on April 23.

For the full press release, please see below.

Press Release (PDF)