U.S. biologists reported on Tuesday that they have discovered a crucial protein link to wound healing, which may help treat severe complications of diseases such as diabetes and eczema at University of California in San Diego (UCSD).
A protein previously linked only to cell death plays a critical role in the healing of wounds in laboratory mice. This protein, known as caspase 8, is deficient in humans with eczema but produced in excess amounts by diabetics, according to their discovery, which will be published in the upcoming issue of journal Nature.
The researchers said their discovery may explain why many diabetics lack normal wound responses and suffer severe complications from minor cuts and scrapes, and why those with eczema exhibit a chronic inflammation of the skin that compromises its protective function.
They examined laboratory mice that have been knocked out the gene in the epidermis necessary for the production of caspase 8. "Not only does the loss of this protein stimulate inflammation, which brings in a rush of cells designed to stop microbes from infecting the wound," said Colin Jamora, the researcher who headed the research team. " But it also stimulates the production of stem cells that provide the materials to help close the wound."
In order to heal wounds, animals have three responses: inflammation, in which the body brings disease-fighting cells to the site of the wound; proliferation, in which stem cells are triggered to produce more skin cells to fill the wound; and remodeling, in which the skin is smoothed over to look as normal as possible.
The research team discovered that the loss of caspase 8 in the epidermis actually releases a protein from the cells called interleukin 1-alpha that can travel deeper into the tissue to recruit immune cells and cause the local reservoirs of stem cells in the skin to start proliferating. This is the first time researchers can demonstrate that caspase 8 triggers the release of this special protein and how it does so.
The UCSD researchers are now studying laboratory mouse models of human diabetes, which produce excess amounts of caspase 8, to determine whether artificial damping of caspase 8 will restore their ability to heal wounds.
"We are also using the caspase-8-knockout mouse as a model system to study eczema in order to identify the players that contribute to this disorder and thereby unveil new therapeutic targets to attack a disease that affects 10 to 20 percent of children worldwide," Jamora said.