Two new UC Davis Health studies explored how differences in skin composition may lead to dermatological conditions, such as psoriasis and atopic dermatitis.
“Skin does not have a uniform composition throughout the body,” said Emanual Maverakis, professor of dermatology, molecular medical microbiology at UC Davis and senior author on both studies. “Different skin characteristics at different body sites may affect the skin’s susceptibility to certain diseases.”
Skin diseases affect about 84.5 million Americans. Aging, trauma, and environmental and genetic factors can lead to a wide range of skin conditions. Body site determines skin structure and function and disease susceptibility
The skin is the largest organ in the body. It has an average area of about 20 square feet - that’s the size of a 4’ by 5’ room! Its outermost layer (epidermis) has a lipid matrix composed of free fatty acids, cholesterol and ceramides (a family of waxy lipid molecules).
This layer must meet the environmental challenges specific to each area of the body. For example, the skin of the face needs to be thin and flexible to accommodate facial expressions. The skin covering the heel of the foot has to be thick and rigid to withstand force and protect it from objects we step on.
Skin composition depends on multiple factors, including the structure of the skin barrier, the cell types, and the genes they express.
Until recently, little was known about the cellular and molecular processes behind these differences. In the first study, researchers showed the mechanisms that lead to these structural changes in the skin.
The epidermis has a “brick and mortar” structure: molecules like ceramides, cholesterol and fatty acids make up the “mortar,” and cells called keratinocytes are the “bricks.”
The researchers used single-cell sequencing to characterize how the keratinocytes differ at different body sites. They also used targeted molecular profiling to characterize the molecules that form the “mortar” between the keratinocytes. They then examined how these differences in gene expression matched the compositional differences in the lipid and protein structures across body sites. These experiments explained why the skin looks so different at different body sites.
The compositional differences in the skin’s lipids and proteins across different body sites may also explain why different skin diseases are found at different body sites. While characterizing the specific lipid alterations associated with various skin diseases, the researchers discovered that lipids stuck to a piece of tape applied to the skin were sufficient to diagnose a patient with a particular skin disease.
“These discoveries will lead to non-diagnostic tests for common dermatologic disease” said co-lead author, Project Scientist Alexander Merleev.
“These differences are also relevant to the future design of skin care products,” said Stephanie Le, dermatology resident and co-lead author of the study. “They demonstrate how skin care products should be specifically formulated to match the particular body site that they will be applied to.”
