Wound Healing Secrets Discovered in Worms May Help Diabetics and the Elderly
Although much is known about the cellular processes skin undergoes during the healing stages of wound repair, the initial skin cell response has remained relatively elusive. Recently, however, scientists report their discovery that the initial stages of wound healing in the tiny nematode roundworm known as C. elegans may hold the key to treating wounds that are especially problematic for diabetics and the elderly.
Biologists from the University of California, San Diego have just announced in a paper to be published in the December issue of the scientific journal Current Biology, their discovery of genes that both promote and inhibit wound healing in the skin of a common roundworm known by its scientific name Caenorhabditis elegans, or C. elegans for short.
C. elegans is a tiny soil-living worm measuring only about 1 millimeter in length that feeds on E. coli bacteria. C. elegans comes in two sexes: male and hermaphrodite. Reproduction is accomplished either through self-fertilization of a hermaphrodite or through sex between a hermaphrodite and a male. C. elegans is a popular animal model for scientific study in part because it is highly fecund, inexpensive to house and possesses a relatively simple genome for genetic study.
However, what makes this wonder worm particularly unique is that it is transparent and the number of cells it possesses is a constant 959 cells. This allows easy study of individual cells within a multicellular organism that is not possible with other animal models for experimentation with exception to the zebra fish animal model.
This cellular transparency of C. elegans is what made it possible for the authors of the paper to discover genes that are involved in wound healing. As it turns out, life in the wild (soil) is hazardous for C. elegans as it feeds on E. coli because of its easily damaged skin. According to a UC San Diego news release, Professor of Biology and lead author Andrew Chisholm, “They have a hydrostatic skeleton in which the skin and muscles are under pressure to allow the animal to stay semi-rigid, so when you jab a worm with a needle it will, in effect, explode,” he said. “But remarkably, they don’t die when you do that because they have evolved ways to very rapidly close wounds to survive in the wild. In their natural environment, their predators try to exploit the worm’s vulnerable exoskeleton. There are a whole group of fungi with tiny spikes that just sit around waiting for the worms to crawl over them so they can poke holes through their cuticle.”
It is the C. elegans ability to recover quickly from a wound that prompted Chisholm and his colleague postdoctoral fellow Suhong Xu, to apply wounds to the worms using lasers and needles and then analyze the cellular processes that occur as the wounds begin to heal.
From previous studies, the researchers knew that when a cell is damaged that it undergoes changes involving calcium molecules. Using time lapse photography and special fluorescent proteins that bind to calcium, they discovered that once injured, calcium molecules near the wound spread out—presumably through channels as a signal to another part of the cell.
“We think the channel is playing an important role in either sensing damage or responding to some other receptor that senses damage,” said Chisholm. “Is it sensing a change in the tension of the cell? Is it sensing some kind of change in electrical potential? We don’t know.”
What they do know, however, is that actin, a common protein in cells that plays a role in muscle contraction, is recruited toward the wound, which then closes the opening of the wound by drawing itself around the wound and contracting on itself in a ring-like structure.
“We think that calcium is regulating this process,” said Chisholm, “because if you knock out calcium with a drug that chelates calcium, essentially locking it up, you don’t get the ring. If you have a genetic mutant worm with low levels of calcium, you don’t get the ring. But if you bathe this mutant in calcium, you can restore this ring.”
In another set of experiments the researchers have also discovered a protein called DAPK-1 that rather than aiding the healing process, actually acts to inhibit wound closure. The authors hypothesize that finding a drug that could counter DAPK-1 effects may in turn improve wound healing in humans.
The importance of their findings is particularly relevant toward treating problematic skin trauma in the elderly and individuals with diabetes.
As they age, the elderly increasingly develop a slower healing process with even the most minor of scratches and cuts. Their skin’s inflammatory and proliferative responses are delayed and their collagen formation is significantly different from when they were younger. In diabetic patients, one complication of their disease is their reduced ability for wound healing. Narrowing of their blood vessels reduces the amount of blood flow to a wound that is needed to support the healing process. This is particularly true for below the knee wounds where swelling adds to the complication of the skin’s difficulty in healing following injury.
“Wound healing in humans is a much more complicated situation than this [C. elegans] of course,” Chisholm said. “But the hope is that by learning more about the basic biology of wound responses, we can eventually learn how to heal wounds more quickly or, in the case of the elderly or those with diabetes, overcome their weakened responses to healing.”
Reference: Current Biology