Skin Signal
Lipid Holds Promise for Skin Diseases, Age-Related Damage
The body may hold a secret to normalizing skin cell growth that is over-zealous in diseases such as psoriasis and too slow in aging and sun-damaged skin, researchers say.
Phosphatidylglycerol, a natural body lipid, appears to signal cells to normalize growth and maturation or differentiation. “When we apply it to skin cells, we see the normalization ability,” said Dr. Wendy B. Bollag, an MCG cell physiologist.
Her research, published online in The Journal of Investigative Dermatolog y, helps piece together the signaling pathway that prompts skin cells to stop multiplying and start differentiating.
Perhaps most importantly, it shows that bypassing that pathway—one researchers suspect becomes dysfunctional in diseases such as psoriasis—and giving the signal itself restores normal differentiation of skin cells.
She and Apeliotus Technologies of Atlanta have received a National Institutes of Health Small Business Technology Transfer grant to test the lipid in animals with mild psoriasis. A Georgia Research Alliance Industry Partnership Grant will allow parallel studies in animal models of chronological aging and photoaging from excessive sun exposure.
Glycerol, a precursor of phosphatidylglycerol, is used in many skin care products to help skin retain moisture. “We think it also has this additional role as a precursor for an important lipid signal in the skin,” said Dr. Bollag.
She’s shown that the channel, aquaporin-3, delivers glycerol to phospholipase D, resulting in the skin cell differentiation signal, phosphatidylglycerol. “That’s good because without it, you get abnormal differentiation in skin diseases such as psoriasis and non-melanoma skin cancer. We think maybe in psoriasis, the phospholipase D and aquaporin-3 become disconnected and can’t produce phosphatidylglycerol. If you only put glycerol on it, it may not help.”
But it looks as though the signal does.
Her newest research, done in mouse skin cells in culture, showed that aquaporin-3 manipulation impacted phosphatidylglycerol generation. “The glycerol was coming through aquaporin. If we blocked it, we stopped glycerol from coming through and we also blocked phosphatidylglycerol. Then we started manipulating the various players. We did some overexpression of aquaporin and showed it promoted differentiated status of the keratinocytes.
“Then we wondered what would happen if we actually gave phosphatidylglycerol itself, so we bypassed the whole aquaporinphospholipase D system and saw some interesting results.”
Phosphatidylglycerol inhibited growth of rapidly growing skin cells and increased growth in slow-growing cells. MCG has a patent pending on the ability of phosphatidylglycerol to normalize skin cell function.
“The key is cells are supposed to proliferate in this one layer,” she says of the basal layer, where a skin cell divides, with one staying to divide again and the other expressing different genes, proteins and functions as it moves toward the surface. Without phosphatidylglycerol, cells can overproliferate and differentiate improperly, Dr. Bollag explained.
“Right before cells reach the layer that we actually see, called the cornified layer, they spit out lipids they synthesize to make the water-permeability barrier, then they basically die. But they leave behind hard shells that give skin its mechanical strength. When you get older, you don’t turn it over as well,” Dr. Bollag said, explaining why despite ongoing cell turnover old skin looks, well, old.
As its name implies, aquaporin also transports water, but researchers have learned it’s a lot better at delivering glycerol.
--Toni Baker