Eight Previously Unknown Wound Response Genes Discovered

Researchers working with a fruit fly (Drosophila) embryo model system for the study of wound healing have identified eight additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair.

Investigators at the University of California, San Diego (USA) sought to establish a broader understanding of the genome-wide transcriptional response at different time points in the epidermis around clean puncture wounds. To do this they developed a protocol using Drosophila embryos that took advantage of trypsin-mediated wounding in conjunction with microarray technology to determine changes in the genes expressed by wounded embryos.

Trypsin is a member of the serine protease family of enzymes that cleaves peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the enzyme's active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serine proteases fall into two broad categories based on their structure: chymotrypsin-like (trypsin-like) or subtilisin-like. In humans, they are responsible for coordinating various physiological functions, including digestion, immune response, blood coagulation, and reproduction.

Results published in the April 24, 2013, online edition of the journal PLOS ONE revealed that by comparing results from microarray analyses of wounded Drosophila embryos with similar results on mammalian skin wounding, it was possible to see which evolutionarily conserved pathways were activated after epidermal wounding in very diverse animals. The innovative trypsin-mediated wounding protocol developed for this study enabled the identification of eight additional genes that were activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggested novel genetic pathways that may control epidermal wound repair. Additionally, the data augmented the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues.

"Many of the key molecules and proteins involved in Drosophila wound healing are involved in mammalian wound healing," said first author Rachel Patterson, graduate student in cell and developmental biology at the University of California, San Diego. "The genetics of Drosophila are not as complicated as mammalian genetics, so it is easier to attribute specific biological functions to individual genes. Perhaps our results can be translated to existing human therapies by incorporating specific, regulated serine proteases and antimicrobial peptides at the sites of diabetic ulcers or skin grafts for more efficient wound healing. Our results might also have application to treating chronic skin diseases such as psoriasis, severe dry skin, and eczema in which levels of these enzymes are known to be abnormal."

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