Every year in the United States, 10,000 patients die and another million are disabled from burn wounds that don't completely heal or result in scarring. Researchers have had a difficult time developing treatments for burn injuries because they had little idea of what genes were involved in healing and at what stages during the healing process they become important.

Dr. David Mozingo and colleagues at the Institute for Wound Research set out to answer this question. As reported in the February 2004 issue of Physiological Genomics, they found that the expression levels of at least 192 genes were changed after the burn. To do this, they used microarrays to measure gene expression levels in normally healing mouse tissues damaged by second degree scald burns at two hours, and three and 14 days following the injury.

The group found that most of the genes were upregulated for at least one timepoint during the study, with only 24 genes being sharply downregulated for the entire 14 days. Gene groups with related functions usually turned on and off together during the same stages of the healing process. What's more, gene expression of wounded cells did not completely return to normal even after 14 days following the injury.

From this analysis, scientists now know what kinds of proteins are involved in sequential stages of wound healing. At two hours following the burn, damaged skin cells upregulate genes responding to heat and stress caused by the injury, as well as those responsible for inflammation around the wound. However, after 3 or 14 days, this response is no longer needed. Now, it becomes important to heal the wound. To do so, several types of genes remain upregulated for up to fourteen days. These include proteases, which break down damaged tissue to pave way for laying down of healthy cells, as well as genes responsible for cell to cell communication.

Using the GeneChip® Murine Genome U74Av2 Set, the group was able to analyze the expression levels of over 12,000 different genes at a time at each of the three timepoints following the burn. By comparison, the most extensive study to date looked at only 588 genes.

Mozingo has taken the first step towards identifying genes that could be targeted by therapies designed to accelerate or slow down burn healing. "Future studies will evaluate how expression patterns may deviate in cases when healing is either delayed or accelerated," says Mozingo. Those studies may give us a precise idea of how to change the expression levels of these genes back to normal, allowing wounds to heal more cleanly and rapidly.