A role for p75 neutrophin receptor in the control of apoptosis-driven hair follicle regression

Vladimir A. Botchkarev, Natalia V. Botchkareva, Kathryn M. Albers, Ling Hong Chen, Pia Welker, Ralf Paus

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Abstract

To examine the mechanisms that underlie the neurotrophin-induced, apoptosis-driven hair follicle involution (catagen), the expression and function of p75 neurotrophin receptor (p75NTR), which is implicated in apoptosis control, were studied during spontaneous catagen development in murine skin. By RT-PCR, high steady-state p75NTR mRNA skin levels were found during the anagen-catagen transition of the hair follicle. By immunohistochemistry, p75NTR alone was strongly expressed in TUNEL+/Bcl2- keratinocytes of the regressing outer root sheath, but both p75NTR and TrkB and/or TrkC were expressed by the nonregressing TUNEL-/Bcl2+ secondary hair germ keratinocytes. To determine whether p75NTR is functionally involved in catagen control, spontaneous catagen development was compared in vivo between p75NTR knockout (-/-) and wild-type mice. There was significant catagen retardation in p75NTR knockout mice as compared to wild-type controls (P<0.05). Instead, transgenic mice-overexpressing NGF (promoter: K14) showed substantial acceleration of catagen (P< 0.001). Although NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3) accelerated catagen in the organ-cultured skin of C57BL/6 mice, these neurotrophins failed to promote catagen development in the organ-cultured p75NTR null skin. These findings suggest that p75NTR signaling is involved in the control of kerotinocyte apoptosis during catagen and that pharmacological manipulation of p75NTR signaling may prove useful for the treatment of hair disorders that display premature entry into catagen.

Original languageEnglish (US)
Pages (from-to)1931-1942
Number of pages12
JournalFASEB Journal
Volume14
Issue number13
StatePublished - Oct 16 2000

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Keywords

  • Alopecia
  • BDNF
  • Kerotinocyte catagen
  • NGF
  • NT-3
  • p75NTR

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Botchkarev, V. A., Botchkareva, N. V., Albers, K. M., Chen, L. H., Welker, P., & Paus, R. (2000). A role for p75 neutrophin receptor in the control of apoptosis-driven hair follicle regression. FASEB Journal, 14(13), 1931-1942.