Our lungs are A-list stars at detecting oxygen, but a new study in mice suggests that the skin may be a key supporting actor. Researchers have found that a mouse's skin can sense oxygen levels in the air and that it helps regulate the number of oxygen-carrying red blood cells in the body. Human skin may behave the same way, which could open the door for new ways to boost blood cell levels for athletes seeking to gain an edge or patients with anemia.
Frogs and other amphibians gauge ambient oxygen concentrations through their skin, but nobody had ever checked to see if mammals had the same ability. Randall Johnson, a molecular biologist at the University of California, San Diego, stumbled on the possibility while conducting a skin cancer experiment on mice. He noticed that animals that lacked a particular skin gene had so many red blood cells that "their blood looked like sludge." This observation suggested that the skin was somehow signaling the body to ramp up production of erythropoietin (EPO), a hormone made in the kidneys that spurs the generation of red blood cells.
To figure out what was happening, Johnson's team deleted the HIF-1α gene, which is activated in response to oxygen deprivation, from the skin of 11 mice. Exposure to low-oxygen air sends EPO levels soaring in normal mice, but these conditions did not induce a rise in the hormone in the animals without HIF-1α, the researchers report in the 18 April issue of Cell. When the scientists applied nitroglycerin patches, which cause increased blood flow to the skin, to nine normal mice breathing air with adequate oxygen, EPO and red blood cell levels shot up, confirming that diverting blood into the skin drives the production of EPO. The researchers don't yet know how the skin senses the gas, but they found that mouse skin contains the same oxygen-sensitive potassium channels as the lung. Humans also carry the HIF-1α gene, so Johnson suspects that our skin may have the same oxygen-sensing capability. If so, he says, this could lead to new, legal ways to boost red blood cell production in athletes, much like using oxygen tents or training at high altitudes. EPO is banned for this use, but exposing only the skin to low-oxygen levels might achieve the same effect, he says.
Desmond Tobin, a cell biologist at the University of Bradford in the U.K., says that the findings, together with a recent study that found that EPO and HIF-1α levels increase in human hair under low-oxygen conditions, support the notion that human skin responds to oxygen. Joachim Fandrey, a physiologist at the University of Duisburg-Essen in Germany, adds that the results suggest that nitroglycerin patches, which have a long track record in treating chest pain in heart disease patients, might boost EPO production in people suffering from anemia due to kidney disease or cancer.
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