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The aim of this study was to identify novel inducers of hair growth using gene expression profiling at various stages of hair-growth induction. First, we analyzed gene expression at the onset of hair growth in mice induced by cyclosporin A (CsA), a well-known hair-growth inducer, using DNA microarray analysis. The results unveiled genes involved in the step-by-step progression of hair growth, including increases in melanin biosynthesis and decreases in immune response at d 2 and the subsequent stimulation of cell proliferation at d 4, followed by the up-regulation of hair specific keratins at d 7 after CsA treatment. With the use of the connectivity map (Cmap), agents that had a similar "gene signature" to that of the profiles of CsA-treated mice were identified. Several agents, including CsA, were identified by the Cmap and were evaluated for hair induction activity in vivo. One of the proposed agents, fluphenazine (from the d 2 signature) actually induced hair growth in vivo (ED50: 2 mM for single application), and the subsequent application of 5 mM iloprost (from the d 4 signature) significantly enhanced the hair-growth effect of fluphenazine. From these results, Cmap analysis was proven to be a useful method that connects gene expression profiles of complicated biological processes, such as hair-growth induction, to effective agents. [ABSTRACT FROM AUTHOR]

The hair cycle is a highly regulated process controlled by multiple factors. Systematic analysis of gene expression patterns in each stage of the hair cycle would provide information useful for understanding this complicated process. To identify genes associated with the hair cycle, we used DNA microarray hybridization to analyze sequential gene expression patterns in mouse skin following hair cycle synchronization by wax depilation. Messenger RNA levels in mouse skin at various times after depilation were compared with those prior to depilation (resting phase). According to their expression patterns, upregulated genes were categorized into four groups: early anagen, middle anagen, late anagen/early catagen, and middle/late catagen, and processes that take place in each stage were evaluated. We identified 12 new components that are specifically expressed in the hair follicle, 11 genes in anagen including carbonic anhydrase 6, cytokeratin 12, and matrix metalloproteinase-11 in catagen that were confirmed using in situ hybridization. The strategy used here allowed us to identify unknown genes or process previously not suspected to have a role in hair biology. These analyses will contribute to elucidating the mechanisms of hair cycle regulation and should lead to the identification of novel molecular targets for hair growth and/or depilation agents. [ABSTRACT FROM AUTHOR]