We do not yet know all the molecular elements involved in fibrotic wound repair. To obtain a comprehensive picture of gene activity in wounded adult skin, transcriptional profiles of fibroblasts or whole skin have been examined. Iyer et al. (1999) analyzed the response of human neonatal foreskin fibroblasts to serum stimulation in vitro. DNA microarray hybridization was used to measure the temporal changes in mRNA levels of over 8,600 genes. Bioinformatic analysis revealed clusters of genes that shared specific expression profiles. The clusters included known genes involved in trans-duction of serum signals, entrance and progression through the cell cycle, and in wound repair, including 10 genes associated with clotting and hemostasis, 8 with inflammation, 6 with re-epithelialization, 12 with angio-genesis, and 19 with remodeling of granulation tissue. The response to serum was rapid, with the most rapid response (within 15 min) exhibited by genes encoding transcription factors and other proteins involved in signal transduction. Over 200 genes in this study were novel, with unidentified function.
In wounded whole human skin, microarray analysis revealed that at 30 min postinjury, 124/4,000 (3%) of the genes in the array were upregulated by two-fold or more (figure 2.6); these genes again were involved primarily in signaling and signal transduction (Cole et al., 2001). By one hour, 46 genes (1.15%) were upreg-ulated and 264 (6.6%) were downregulated two-fold or more. Analysis of a cDNA library made by subtraction between unwounded and wounded mouse back skin o
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