Unraveling the mechanism of skin barrier formation

April 14, 2017

Scientists have identified the gene responsible for generating acylceramide, the key lipid in forming the skin barrier that protects us from pathogens, allergens and other harmful substances. This finding could prove crucial in developing medicines for treating atopic dermatitis and ichthyosis.

Defects of the can trigger skin diseases such as atopic dermatitis, which is said to afflict about 10 percent of the population in some developed countries. Acylceramide, a lipid only found in skin, plays a pivotal role in forming this barrier. Although most of the genes needed to generate this special lipid have been recently identified, the gene responsible in the final step to produce acylceramide has been missing. Finding the last piece in the puzzle, therefore, was essential for elucidating the skin barrier's molecular mechanism.

The team led by Professor Akio Kihara at Hokkaido University established a cell system that produces the acylceramide precursor ω-hydroxyceramide and used it to evaluate the activity of several candidate genes to produce acylceramide. The research methodology addressed a long-standing hurdle in experiments using epidermal keratinocytes which caused the inefficiency of gene delivery to the cells. By using other type of cultured cells transfected with the required for other steps of acylceramide synthesis, the team has overcome the issue and tested the function of the .

As a result, the team succeeded in finally identifying the key gene as PNPLA1. The researchers also found evidence that suggests the lipid triglyceride acts as a linoleic acid donor. Furthermore, they discovered that mutant PNPLA1 proteins found in patients with ichthyosis, a serious genetic skin disorder characterized by dry and scaly skin, show reduced or no enzyme activity.

As there is no curative treatment for , patients are currently given only symptomatic therapies. No treatment has been established for ichthyosis. "To better treat such patients, it is essential to restore the functions of the skin barrier," says Akio Kihara. "Having unraveled the of acylceramide synthesis, our study should enable the search for compounds that boost acylceramide synthesis and therefore restore the skin barrier."

This study was conducted as a part of a project under the Advanced Research and Development Programs for Medical Innovation (AMED-CREST) of the Japan Agency for Medical Research and Development.

Explore further: Discovery of a new metabolic pathway of a known lipid has implications in cancer, obesity

More information: Yusuke Ohno et al. PNPLA1 is a transacylase essential for the generation of the skin barrier lipid ω-O-acylceramide, Nature Communications (2017). DOI: 10.1038/NCOMMS14610

Related Stories

Discovery of a new metabolic pathway of a known lipid has implications in cancer, obesity

March 10, 2017
A collaborative Stony Brook University research team has discovered a novel metabolic pathway of the lipid ceramide, which is involved in cell death. The finding illustrates that ceramide is stored in lipid droplets, a step ...

Altered lipids, skin infections may point to new personalized therapy for atopic dermatitis

March 8, 2017
Researchers have discovered a new way to identify the lipids, or fats found in the skin of people who have atopic dermatitis, and compare them to people with healthy skin.

Phthalate, paraben levels up in children with atopic dermatitis

March 21, 2017
(HealthDay)—Children aged 4 to 9 years with atopic dermatitis and with frequent use of emollients have increased urinary levels of low-molecular weight (LMW) phthalate metabolites and parabens, according to a study published ...

Why air pollutants make some people vulnerable to atopic dermatitis

November 23, 2016
Tohoku University Graduate School of Medicine and Tohoku Medical Megabank Organization (ToMMo) are pleased to announce the published results of a study into why air pollutants cause some people to be more susceptible to atopic ...

People susceptible to atopic dermatitis have different microbes living on their skin than non-sufferers

July 27, 2016
Microbial communities living on the skin of people susceptible to the skin disease atopic dermatitis differ from those of healthy individuals. This finding by A*STAR researchers provides insight into the roles that resident ...

Skin defences point to eczema therapies

October 4, 2016
The body's own natural defences could be harnessed in a potential therapy for a common skin condition, research suggests.

Recommended for you

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Zika-related nerve damage caused by immune response to the virus

November 20, 2017
The immune system's response to the Zika virus, rather than the virus itself, may be responsible for nerve-related complications of infection, according to a Yale study. This insight could lead to new ways of treating patients ...

Breast milk found to protect against food allergy

November 20, 2017
Eating allergenic foods during pregnancy can protect your child from food allergies, especially if you breastfeed, suggests new research from Boston Children's Hospital. The study, published online today in the Journal of ...

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

How a poorly explored immune cell may impact cancer immunity and immunotherapy

November 17, 2017
The immune cells that are trained to fight off the body's invaders can become defective. It's what allows cancer to develop. So most research has targeted these co-called effector T-cells.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.