Brief report: Requirement of TACE/ADAM17 for hair follicle bulge niche establishment

Keisuke Nagao, Tetsuro Kobayashi, Manabu Ohyama, Haruhiko Akiyama, Keisuke Horiuchi, Masayuki Amagai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Hair follicles (HFs) are equipped with stem cell niches that allow regeneration. Tumor necrosis factor-α converting enzyme (TACE), also known as A disintegrin and metalloproteinase 17, is a proteolytic enzyme that regulates a variety of cell surface molecules including TNF-α, via ectodomain shedding. We found TACE expression on mouse HFs and conditionally depleted it in cells that expressed sex-determining region Y-related high-mobility-group box 9 (SOX9) transcription factor, an HF stem cell transcription factor (Taceflox/flox-Sox9-Cre, hereafter, "Tace/Sox9"). Tace/Sox9 mice were born with brittle hair with prolonged anagen phase. They underwent diffuse, progressive, and ultimately whole-body hair loss by 20 weeks old. Tace/Sox9 HFs lacked CD341 bulge cells as demonstrated via immunofluorescence microscopy and flow cytometry. Realtime PCR revealed downregulation of transcription factors Sox9, Lhx2, and Gata3 and upregulation of Lef1. In vitro colony-forming capacity was abolished in Tace/Sox9 keratinocytes, and HFs exhibited increased proliferation in situ, collectively demonstrating that Tace/Sox9 mice failed to establish the bulge niche and to maintain "stemness" of HF stem cells. Epidermal growth factor receptor (EGFR) signaling was impaired in Tace/Sox9 keratinocytes, and mice depleted of Egfr in SOX9-expressing tissues exhibited hair phenotype nearly identical to Tace/Sox9 mice, demonstrating EGFR signaling as a pathway downstream of TACE in HF homeostasis. This study provides mechanistic implication for human TACE-deficiency and for hair abnormality caused by EGFR inhibitors.

Original languageEnglish
Pages (from-to)1781-1785
Number of pages5
JournalStem Cells
Volume30
Issue number8
DOIs
Publication statusPublished - 2012 Aug 1

Keywords

  • Alopecia
  • Hair
  • Hair follicles
  • SOX9
  • Stem cells
  • TACE/ADAM17

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Nagao, K., Kobayashi, T., Ohyama, M., Akiyama, H., Horiuchi, K., & Amagai, M. (2012). Brief report: Requirement of TACE/ADAM17 for hair follicle bulge niche establishment. Stem Cells, 30(8), 1781-1785. https://doi.org/10.1002/stem.1153