Glycerin May Help Skin Disease, Study Finds

Glycerin, or glycerol, is a natural alcohol and water attractor that's been used in skin care products for centuries, says Dr. Wendy Bollinger Bollag, cell physiologist.

In research published in the December issue of The Journal of Investigative Dermatology, she and co-author Dr. Xiangjian Zheng, who worked as a graduate student in her lab and is now a postdoctoral fellow at Vanderbilt University, show that glycerol also makes skin look and function better by helping skin cells mature properly.

"This is a pretty novel hypothesis that is really quite in its infancy," Dr. Bollag says of the finding that glycerol works as a signal to help direct skin cells through their four normal stages of maturity. In the endless cycle of skin-cell production, the youngest cells move up from the deepest layer and switch from replicating as their main function to eventually becoming mature surface cells that spit out lipids to help form the skin's protective barrier before they die.

The researchers' findings about the signaling function of glycerol means the readily available fluid, found in its pure state on grocery store shelves and as a component of many other products, may help people with diseases such as psoriasis and non-melanoma skin cancers, that result from abnormal proliferation and maturation of skin cells, and may augment wound-healing.

The researchers found glycerol's role in skin cell maturation while studying phospholipase D, an enzyme that converts fats or lipids in the external, protective cell membrane to cell signals. Phospholipids are fats found throughout the body that make up much of the plasma membrane lipid bilayer that encases each cell and helps keep it from mixing with other cells. All cells have this layer and skin cells secrete extra lipids which help provide an additional barrier. "Think about it," Dr. Bollag says. "If there was not some sort of barrier, when you took a bath, all the water would go into you and you would blow up like a balloon."

Knowing that phospholipase D can use alcohols, such as ethyl alcohol, Drs. Bollag and Zheng wondered what it would do with glycerol, a physiological alcohol used to synthesize fat and subsequently released during exercise as fat fuels physical exertion.

What they found is that when phospholipase D pairs with glycerol, it produces a distinctive signal that directs skin cell maturation, Dr. Zheng says.

They found that, despite its name, a channel called aquaporin 3, which is expressed in skin cells and allows only certain molecules through, is not particularly good at transporting water but is good at transporting glycerin. Inside skin cells, aquaporin 3 and phospholipase D interact. "We don't know if it's direct or if there is an intervening protein, but they associate," Dr. Zheng says. They theorize that aquaporin 3 funnels glycerol to phospholipase D, resulting in phosphatidylglycerol, a lipid that appears to signal enzymes involved in skin cell differentiation, Dr. Zheng says.

"We think the glycerol is serving as a substrate to allow the skin to mature properly and, when you don't have enough glycerol in the skin, cells don't mature properly and that is why you get hyper-proliferative, thick skin," Dr. Bollag says.

A mouse model for dry, flaky, unnaturally thick and slow-healing skin recently developed by researchers at the University of California, San Francisco, may help prove the Augusta researchers correct.

The genetically manipulated mice lack sufficient glycerol in their skin because they are missing the gene responsible for aquaporin 3. "That is why their levels of glycerol are reduced, because they don't have that glycerol channel," Dr. Bollag says. The mouse research was published in the Journal of Investigative Dermatology about the same time Drs. Bollag and Zheng were submitting their work. "We were thinking, we know why this happens," Dr. Bollag says. Water-loving glycerol couldn't get inside the phospholipase D cell without a channel. Consequently, the phosphatidylglycerol that results from their union doesn't happen and neither does the resulting signal that directs normal skin cell maturation.

Another naturally occurring mouse with dry, thick skin has aquaporin 3 but lacks skin fats that are normally broken down to release glycerol, Dr. Bollag says.

When glycerol was given topically or orally to these animal models, many of the skin problems resolved. Other water-attracting agents didn't work so well, which gives the MCG researchers more fuel for their finding that glycerol also plays a key role in normal skin cell maturation and proliferation.

They hope their findings will not only contribute to a better understanding of normal skin development but lead to more effective treatment when development is abnormal.

"For instance, in psoriasis, you have keratinocytes (skin cells) that grow too much and if we could somehow harness this signal, we might somehow be able to tell those keratinocytes, 'No. It's time to mature. Stop growing. Mature and form good skin. Form this good barrier,'" Dr. Bollag says. "Another instance in which you don't get normal maturation of the keratinocytes is in skin cancer, the non-melanoma skin cancers. So here is another way that if we could potentially harness this signaling pathway, we could maybe bypass the signal that basically makes them cancer and tell them, 'No. Mature and form skin and that's it. Don't become a cancer,'" says Dr. Bollag.

The MCG researcher has submitted a grant application to the National Institutes of Health to further study the signaling mechanism she and Dr. Zheng have found. The NIH supported her current studies as well.

"(Now we are) trying to find out what the signal activates," she says. "In other words, how does the signal that is produced by phospholipase D and the glycerol actually tell the cell to mature? How does that signal then activate certain enzymes and proteins in the cell to make the cell mature? Other things we are interested in looking at are ways to manipulate the system, for instance to increase signal formation, to see if we can then increase keratinocyte formation and that would potentially be a way to harness the system to treat skin diseases."