U.S. Department of Health and Human Services

Skin Strikes a Balance Between Growth and Integrity

A new study in mice has discovered that a molecule called sphingosine-1-phosphate (S1P) is an important—and sometimes vital—regulator of the skin’s lifecycle. Skin cells are constantly growing, differentiating (producing specialized types of cells), dying, and being shed. Disruptions in this cycle can lead to diseases where skin is too thick or too thin. 
Mice lacking the gene for a protein that controls S1P had abnormally high S1P levels and stunted growth compared to normal mice when examined within a few days after birth. They also had serious skin abnormalities—the mutant animals had enhanced skin cell differentiation, which made their skin thicker than normal and prone to peeling and sloughing off. Many of these mice died by three weeks of age, and the few that survived to adulthood had skin abnormalities throughout their lives. Further analysis of the animals’ skin cells demonstrated that increased S1P levels had wide-ranging effects, affecting the activity of over 700 genes, many of which are involved in skin cell differentiation. Therefore, this research suggests that S1P metabolism plays a key role in skin cell differentiation. These indings, if conirmed in humans, may lead to new treatments for skin diseases caused by abnormal skin cell differentiation, such as psoriasis.

Allende ML, Sipe LM, Tuymetova G, Wilson-Henjum KL, 
Chen W, and Proia RL. Sphingosine-1-phosphate 
phosphatase 1 regulates keratinocyte differentiation and 
epidermal homeostasis. J Biol Chem 288: 18381-18391, 2013.