Identification of novel hair-growth inducers by means of connectivity mapping

  • Yumiko Ishimatsu-Tsuji, Shiseido Innovative Science Research & Development Center, Japan
  • Tsutomu Soma, Shiseido Innovative Science Research & Development Center, Japan
  • Jiro Kishimoto, Shiseido Innovative Science Research & Development Center, Japan

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 cyclosporine 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 day 2, the subsequent stimulation of cell proliferation at day 4, followed by the up-regulation of hair specific keratins at day 7 after CsA treatment. Using the Connectivity Map (Cmap) (Lamb J. et al. Science 313, 1929-1935, 2006), agents which 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 day 2 signature) actually induced hair growth in vivo (ED50:2mM for single application), and the subsequent application of 5mM iloprost (from the day 4 signature) significantly enhanced the hair growth effect of fluphenazine. From these analyses, we could identify unexpected novel inducers of hair growth and suggested that Cmap analysis is a useful method which connects gene expression profiles of complicated biological processes, such as hair growth induction, to effective agents.