Researchers have been observing how wounds heal in fruit fly larvae in an attempt to better understand human wound healing. They have found that the formation of scabs and the regeneration of skin after a puncture wound seem to be controlled by two different genetic mechanisms.Mark Krasnow and Michael Galko of Stanford University chose to study the wound healing of fruit flies because there are similarities between their healing process and the human healing process. In both, new skin grows under the scab formed at the wound site and a biochemical pathway for the protein “Jun N-terminal kinase” (JNK) is activated.
In their experiments Krasnow and Galko used a needle the diameter of an eyelash to puncture the cuticle (outer layer) and epidermis layers of fruit flies. They also pinched the skin of other flies to create scabless wounds. Because they wanted to observe the skin healing, they were careful to make these wounds nonfatal.
The researchers studied the wounds and analyzed the genetic changes that happened in the cells as the flies healed. They were most interested in two parts of the process, the formation of scabs and the generation of new skin under the scabs. They were also interested in how the two processes affect each other.
The researchers discovered that the first step in healing a puncture wound was the rapid plugging of the wound to prevent bleeding. This occurred within an hour of the puncture. In the next two to three hours, part of that plug changed to form a scab, which prevented blood loss, protected against infection, and stabilized the wound site. Within three days, the wound had healed and the fly larvae returned to their normal appearance.
At the same time all of this was happening, epidermal cells surrounding the wound site reshaped and reoriented themselves to reestablish the epidermal layer underneath the scab. This layer of skin was regenerated within 24 hours of the puncture.
When the researchers inhibited the process of epidermal spreading, they found that the scab formation was not affected. Conversely, when they blocked scab formation in the puncture wounds, the skin was unable to heal properly. However, although no scabs formed in the pinch wounds (because they did not bleed), the epidermal spreading continued as normal. The researchers surmised from this that the scab formation and epidermal spreading were controlled by two different biochemical processes and that one of the main functions of scabs in puncture wounds was to provide stability during the healing process.
Obviously there are differences in the healing processes of flies and humans. Their skin and skeletal makeup are very different from or own. Additionally, in humans the process takes longer and is more complex. However, Kraznow and Galko hypothesize that wound healing is an ancient process that predates the evolutionary split between mammals and insects, so the process is actually very similar between the two groups of animals. This claim is supported by the fact that, despite our differences, humans and fruit flies share many disease-related genes.
This knowledge about wound healing may prove especially helpful for understanding non-healing foot ulcers in diabetics. It also offers insight into how to reduce scarring after surgery. As scientists discover more about the way wounds heal, they may be able to improve the healing process.
Krasnow and Galko’s findings were published in the August 2004 issue of the online, open-access journal PLoS Biology.
