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Deconstructing Wound Repair
30 September 2003 (All day)
Wounds heal much faster when scientists block a specific protein in the skin, a new study has found. Although it's not clear exactly how the treatment works, the research could have broad significance not only for skin injuries such as deep cuts and burns, but also for internal injuries ranging from spinal cord lesions to corneal abrasions.
Most scientists believe that wounds need to trigger a powerful inflammatory response from the immune system in order to heal. Developmental biologist David Becker at University College London wondered about the role that tiny junctions between cells play in this immune response. Proteins called connexins populate these gap junctions. Becker and his colleagues in London and at the University of Auckland in New Zealand focused on connexin 43, which congregates at an injured site within hours; it's thought to help blood vessels dilate, boosting the number of white blood cells that can travel to the site. These cells launch the body's inflammatory response to injury.
To test whether connexin 43 was a big player in wound repair, Becker's group formulated a special gel containing short stretches of RNA. This "antisense" RNA was the genetic mirror image of the connexin 43 gene and designed to blunt its activity. The researchers applied the gel to skin wounds on the backs of mice.
To their surprise, having less connexin 43 seemed like a good thing: The treated animals healed 50% faster than control mice. The researchers also found that, intriguingly, the gel cut by 20% the number of white blood cells that zoomed up to a wound, the team reports in the 30 September issue of Current Biology. This suggests that inflammation doesn't necessarily speed wound healing. And once the gel diffused through skin and into the bloodstream, the researchers found, the antisense quickly broke down, suggesting that it wouldn't impact other tissues.
"It is certainly new," says Harvard University cell biologist Daniel Goodenough. Although some scientists have experimented with connexins and wounds, none has shown that disrupting one speeds up healing, he adds. Becker's team is now applying the gel to other body tissues; they've already found that injecting it into spinal cord and brain lesions, or into an injured cornea, also facilitates the normal healing process.