Spotlight on Research 2012

August 2012

Researchers Gain New Insights into How High Retinoic Acid Levels Affect Skin Development

For decades, retinoic acid, a product of vitamin A processing, has been a popular ingredient in skin creams designed to reduce the appearance of lines and wrinkles and to clear acne. At too high concentrations, however, retinoic acid in skin creams has been shown to damage the skin. Now research shows high levels of naturally occurring retinoic acid in the skin of mouse embryos can also cause damage during development.

This discovery, led by scientists within the intramural program of the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and published in the Journal of Cell Science, offers new insight into embryonic skin development. The findings could eventually lead to a better understanding of and treatments for a variety of skin conditions.

To understand the effects of high retinoic acid levels on embryonic skin development, researchers in Dr. Maria Morasso’s Laboratory of Skin Biology at the NIAMS used a strain of mice genetically engineered to lack a protein called Cyp26b1. Cyp26b1 is an enzyme that degrades retinoic acid, and thus is one of the regulators of retinoic acid concentrations within the cell. When the enzyme is absent, retinoic acid rises. The elevated level, they found, was not a good thing. High retinoic acid during development resulted in abnormalities in the epidermis — the outermost layer of the skin — and also interfered with the normal function of the skin barrier, which protects against organisms and allergens.

One of the final steps in skin formation during embryo development is the sloughing of the periderm. “We believe that the periderm serves as a transient barrier while the underlying skin is being formed,” says Dr. Morasso. “And once the barrier of the skin is formed, the periderm is sloughed off.”

When retinoic acid levels were high, however, the periderm was retained and the skin barrier was completely defective, says Dr. Morasso. “At this moment, it is not clear how to correlate this with humans, but we can say that in embryonic mouse skin development, it is essential to have a controlled level of retinoic acid.”

Moving forward, scientists hope to gain a better understanding of and to develop potential treatments for abnormal skin development and barrier dysfunction associated with conditions ranging from hypothermia and perinatal dehydration to atopic dermatitis.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

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Okano J, Lichti U, Mamiya S, Aronova M, Zhang G, Yuspa SH, Hamada H, Sakai Y, Morasso MI. Increased retinoic acid levels through ablation of Cyp26b1 determine the processes of embryonic skin barrier formation and peridermal development. J Cell Sci. 2012 Apr 1;125(Pt 7):1827-36. Epub 2012 Feb 24.