Identification of novel hair-growth inducers by means of connectivity mapping.
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 (ED(50): 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.
Ishimatsu-Tsuji
Yumiko
Y
Shiseido Innovative Science Research and Development Center, 2-12-1, Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-8643, Japan.
Soma
Tsutomu
T
Kishimoto
Jiro
J
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H
D016572:Cyclosporine