COMPARISON OF NORMAL HUMAN SKIN GENE EXPRESSION USING CDNA MICROARRAYS

Perturbations in normal wound healing may be traced to perturbations in gene expression in uninjured skin. In order to decipher normal and abnormal genetic responses to cutaneous injury, baseline gene expression in uninjured skin must first be defined. There is little data on gene expression profiles of normal human skin, i.e., which genes tend to be variable in expression and which tend to remain comparable. Therefore this study was designed to determine the degree of variability in human skin mRNA expression. Samples of normal skin were obtained from 9 healthy females undergoing breast reduction surgery. RNA was extracted, reverse transcribed into radiolabeled cDNA and hybridized onto cDNA microarrays of approximately 4400 genes. Gene expression intensities from the 9 samples were normalized and compared as a ratio of highest/lowest expression intensity. Deviation greater than 2 standard deviations from the mean of each gene was used as a cut-off. Seventy-one genes (1.7%) were substantially variable in their expression. These included genes coding for transport proteins, gene transcription, cell signaling proteins, and cell surface proteins. We found minimal variability in the matrix genes, growth factor genes and other groups of genes that are the most often studied in wound healing research. A small but definite variability in gene expression across 9 samples of clinically comparable specimens of normal skin was detected. This is in keeping with clinical observations of the variability in normal skin across individuals. These data provide high-throughput comparison of normal skin gene expression and suggest new molecules that may be studied in skin biology and perhaps, wound repair.