New Study Reveals Mystery of Healthy Skin Barrier Formation | Health
Experts in human genetics and asthma research at Cincinnati Children's Hospital have uncovered important things that happen inside the cell to maintain the barrier that our skin forms to protect us. The far-reaching findings could eventually lead to new ways to prevent and treat inflammatory skin diseases such as eczema and psoriasis.
The skin is the body's largest organ, providing the first line of defense against infection and many other threats to our health. Decades of research have shown that a wide range of diseases can occur, or become worse, when the skin fails to form an effective barrier.
The study was published on August 6, 2024 in the journal Cell ReportsThe team of 22 researchers was led by Dr. Stanley Devore, a specialist in human genetics and asthma research at Cincinnati Children's Hospital.
How does skin protect us?
Human skin supports internal balance by preventing water loss from the body and preventing the penetration of substances from outside the body into it. The upper layer of the skin (stratum corneum) forms a physical barrier that separates the body from its surroundings, and the structure of this layer consists of a fatty substance located between dead and hard cells.
“Our research discovered a previously unknown cellular pathway involving a protein called CARD14,” says Devore. “When this protein is working properly, it maintains a healthy skin barrier, but when it’s not working properly, it promotes the development of skin diseases. We found that CARD14 directly binds to and regulates another protein involved in controlling cell growth and can contribute to cancer when a protein called MYC malfunctions.”
Dr. Devore added:According to the Eurek Alert website“Our study shows that the correct interaction between these two proteins is important for maintaining the skin barrier and protecting against eczema and psoriasis. Given that MYC is linked to cancer, our results also suggest that dysfunction of this signaling pathway may contribute to certain types of cancer throughout the body.”
What are cellular pathways?
A pathway is generally defined as a series of events within a cell. A cellular pathway is a series of actions between molecules in a cell that result in a specific product or change in the cell. These pathways are essential for cell survival, function, and communication with other cells. Cellular pathways often involve a series of biochemical reactions, facilitated by enzymes and other proteins. These pathways can be triggered by external signals (such as hormones, nutrients, or environmental stimuli) or internal signals (such as DNA damage).
New track
The CARD14 gene provides instructions for making a protein that activates a group of interacting proteins known as nuclear factor kappa-B (NF-κB). The NF-κB protein complex regulates the activity of many genes, including those that control the body's immune and inflammatory responses.
Inflammation is a normal response of the immune system to injury and foreign invaders (such as bacteria). The nuclear factor kappa B complex also protects cells from certain signals that would otherwise cause them to self-destruct (undergo apoptosis).
The study's co-authors say that CARD14 regulates skin barrier function through two mechanisms: stimulating nuclear factor kappa B to create an antimicrobial barrier and stimulating MYC to help build a physical barrier.
Previous research has focused on the CARD14-nuclear factor kappa-B signaling pathway, which is thought to promote psoriasis when elevated and eczema when decreased. These inflammatory skin diseases affect millions of people.
However, “this model does not fully explain the variability in disease caused by CARD14,” says Hershey, who directs the Asthma Research Division at Cincinnati Children’s Hospital. “This new CARD14-MYC signaling pathway strengthens the link between CARD14 and skin barrier health. Its signaling regulates MYC function in the most common type of skin cell.”
The study explores how different mutations in CARD14 can promote different skin diseases, including eczema and psoriasis. Importantly, the study suggests that changes in CARD14-MYC signaling can affect barrier function and allergic diseases in other tissues, contributing to asthma by affecting the tissue lining, and this new pathway may also contribute to some types of cancer.
Next steps
“Research is underway to identify small molecule agents that can safely affect the CARD14-MYC pathway,” says Devore. “In fact, some aspects of the study are included in a recent patent application.”
“Our ultimate goal is to develop new treatments,” he adds. “We are also conducting studies to identify cancers that may be affected by CARD14-MYC signaling.”
The co-authors plan to share their findings at a joint conference of the American Society of Allergy, Asthma & Immunology and the World Allergy Organization, to be held from February 28 to March 3, 2025, in San Diego.