Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion

Xuemei Tong, Pierre A. Coulombe

Research output: Contribution to journalArticle

Abstract

Mammalian hair follicles cycle between stages of rapid growth (anagen) and metabolic quiescence (telogen) throughout life. Transition from anagen to telogen involves an intermediate stage, catagen, consisting of a swift, apoptosis-driven involution of the lower half of the follicle. How catagen is coordinated, and spares the progenitor cells needed for anagen re-entry, is poorly understood. Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb. Here we show that this abnormal apoptosis reflects premature entry into catagen. Of the proapoptotic challenges tested, K17-null skin keratinocytes in primary culture are selectively more sensitive to TNFα. K17 interacts with TNF receptor 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent signal relay, suggesting a functional link between this keratin and TNFα signaling. The activity of NF-θB, a downstream target of TNFα, is increased in K17-null skin. We also find that TNFα is required for a timely anagen-catagen transition in mouse pelage follicles, and that its ablation partially rescues the hair cycling defect of K17-null mice. These findings identify K17 and TNFα as two novel and interdependent regulators of hair cycling.

Original languageEnglish (US)
Pages (from-to)1353-1364
Number of pages12
JournalGenes & development
Volume20
Issue number10
DOIs
StatePublished - May 15 2006

Fingerprint

Keratin-17
Hair Follicle
Hair
Apoptosis
TNF Receptor-Associated Death Domain Protein
Skin
Tumor Necrosis Factor Receptors
Alopecia
Keratins
Keratinocytes
Stem Cells
Parturition
Growth

Keywords

  • Anagen
  • Apoptosis
  • Catagen
  • Hair cycle
  • Intermediate filament

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion. / Tong, Xuemei; Coulombe, Pierre A.

In: Genes & development, Vol. 20, No. 10, 15.05.2006, p. 1353-1364.

Research output: Contribution to journalArticle

Tong, Xuemei ; Coulombe, Pierre A. / Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion. In: Genes & development. 2006 ; Vol. 20, No. 10. pp. 1353-1364.
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