Inflammatory Mediator TAK1 Regulates Hair Follicle Morphogenesis And Anagen Induction Shown By Using Keratinocyte-Specific TAK1-Deficient Mice

Koji Sayama, Kentaro Kajiya, Koji Sugawara, Shintaro Sato, Satoshi Hirakawa, Yuji Shirakata, Yasushi Hanakawa, Xiuju Dai, Yumiko Ishimatsu-Tsuji, Daniel Metzger, Pierre Chambon, Shizuo Akira, Ralf Paus, Jiro Kishimoto, Koji Hashimoto

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Transforming growth factor-b-activated kinase 1 (TAK1) is a member of the NF-kB pathway and regulates inflammatory responses. We previously showed that TAK1 also regulates keratinocyte growth, differentiation, and apoptosis. However, it is unknown whether TAK1 has any role in epithelial-mesenchymal interactions. To examine this possibility, we studied the role of TAK1 in mouse hair follicle development and cycling as an instructive model system. By comparing keratinocytespecific TAK1-deficient mice (Map3k7fl/flK5-Cre) with control mice, we found that the number of hair germs (hair follicles precursors) in Map3k7fl/flK5-Cre mice was significantly reduced at E15.5, and that subsequent hair follicle morphogenesis was retarded. Next, we analyzed the role of TAK1 in the cyclic remodeling in follicles by analyzing hair cycle progression in mice with a tamoxifen-inducible keratinocyte-specific TAK1 deficiency (Map3k7fl/flK14-Cre-ERT2). After active hair growth (anagen) was induced by depilation, TAK1 was deleted by topical tamoxifen application. This resulted in significantly retarded anagen development in TAK1-deficient mice. Deletion of TAK1 in hair follicles that were already in anagen induced premature, apoptosis-driven hair follicle regression, along with hair follicle damage. These studies provide the first evidence that the inflammatory mediator TAK1 regulates hair follicle induction and morphogenesis, and is required for anagen induction and anagen maintenance.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalPloS one
Volume5
Issue number6
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Sayama, K., Kajiya, K., Sugawara, K., Sato, S., Hirakawa, S., Shirakata, Y., Hanakawa, Y., Dai, X., Ishimatsu-Tsuji, Y., Metzger, D., Chambon, P., Akira, S., Paus, R., Kishimoto, J., & Hashimoto, K. (2010). Inflammatory Mediator TAK1 Regulates Hair Follicle Morphogenesis And Anagen Induction Shown By Using Keratinocyte-Specific TAK1-Deficient Mice. PloS one, 5(6), 1-9. https://doi.org/10.1371/journal.pone.0011275