A ground-breaking USC study explaining how skin heals wounds recently received special recognition in Science and Nature magazines.
The study, “A ‘traffic control’ role for TGFß3: Orchestrating dermal and epidermal cell motility during wound healing,” appeared in the Journal of Cell Biology in March, 2006. It received an “editor’s choice” recognition in Science (312:162, 2006) and was lauded as a “selected article” in the March 11 issue of Nature.
In the study, Wei Li, professor of dermatology, and David T. Woodley, professor and chair of the Department of Dermatology at the Keck School of Medicine, and their colleagues explained the elusive mechanism for sequential migration of human epidermal and dermal cells during wound healing.
The designations by Science and Nature mean the research is considered “a landmark work,” Li said.
“Proper wound healing requires orderly migration of multiple skin cell types, specifically epidermal versus dermal cells,” Li said. The first responders are cells known as epidermal keratinocytes, which move toward the wound and form a new surface layer of skin (epidermis).
Then the dermal cells migrate into the wound below the surface epidermis to begin forming new dermal connective tissue such as collagen, a process called remodeling. In addition, blood vessel dermal cells migrate at the same time into the wound bed to form new blood vessels, a process called angiogenesis.
“Basically we’re talking about one of the mysteries of skin wound healing: whether and, more importantly, how the different types of skin cells move in order to close and then heal the wound,” Woodley said.
Li, and Woodley, together with their research colleagues Balaji Bandyopadhyay, Jianhua Fan, Shengxi Guan, Yong Li, and Mei Chen, wrote that cell migration is a rate-limiting event in skin wound healing. In unwounded skin, cells are nourished by plasma.
When skin is wounded, resident cells encounter serum for the first time. As the wound heals, the cells experience a transition from serum back to plasma.
“This study shows for the first time that a physiological role for the naturally occurring plasma-serum-plasma transition during wound healing is to orchestrate the orderly migration of dermal and epidermal cells” said Woodley.
Mechanistically, the researchers found serum contains transforming growth factor-ß3 (TGFß3), while plasma does not. They report that human serum selectively promotes epidermal cell migration and halts dermal cell migration.
In contrast, human plasma promotes dermal but not epidermal cell migration. The on-and-off switch is operated by TGFß3 levels, which are undetectable in plasma and high in serum, and by type II TGFß receptor levels, which are low in epidermal cells and high in dermal cells.
Understanding the mechanisms of the normal wound healing process could be pivotal to helping wounds that fail to heal, such as wounds in diabetics and the elderly.
“Now we can look into it and see if TGFß3 is significantly reduced or not, to see if this is a mechanism to help wounds heal,” said Li and Woodley. “We don’t want to say TGF ß3 can be added to all non-healing wounds—it’s too early to say—but this is a start.”
B. Bandyopadhyay, J. Fan, S. Guan, Y. Li, M. Chen, D.T. Woodley, W. Li, “A ‘traffic control’ role for TGFß3: Orchestrating dermal and epidermal cell motility during wound healing,” Journal of Cell Biology, April 2006 Volume 172 number 7, 1093-1105.