p75 neurotrophin receptor-mediated signaling promotes human hair follicle regression (catagen)

Eva M.J. Peters, Marit G. Stieglitz, Christiane Liezman, Rupert W. Overall, Motonobu Nakamura, Evelyn Hagen, Burghard F. Klapp, Petra Arck, Ralf Paus

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Nerve growth factor (NGF) and its apoptosis-promoting low-affinity receptor (p75NTR) regulate murine hair cycling. However, it is unknown whether human hair growth is also controlled through p75NTR, its high-affinity ligand pro-NGF, and/or the growth-promoting high-affinity NGF receptor tyrosine kinase A (TrkA). In microdissected human scalp anagen hair bulbs, mRNA for NGF, pro-NGF, p75NTR, and TrkA was transcribed. Immunohistomorphometry and in situ hybridization detected strong NGF and pro-NGF expression in terminally differentiating inner foot sheath keratinocytes, whereas TrKA was co-expressed with p75NTR in basal and suprabasal outer root sheath keratinocytes. During spontaneous catagen development of organ-cultured human anagen hair follicles, p75NTR mRNA levels rose, and p75NTR and pro-NGF immunoreactivity increased dramatically in involuting compartments primarily devoid of TrkA expression. Here, TUNEL+ apoptotic cells showed prominent p75NTR expression. Joint pro-NGF/NGF administration inhibited hair shaft elongation and accelerated catagen development in culture, which was antagonized by co-administration of p75NTR-blocking antibodies. In addition, mRNA and protein expression of transforming growth fector-β2 increased early during spontaneous catagen development, and its neutralization blocked pro-NGF/NGF-dependent hair growth inhibition. Our findings suggest that pro-NGF/NGF interacts with transforming growth factor-β2 and p75NTR to terminate anagen in human hair follicles, implying that p75NTR blockade may alleviate hair growth disorders characterized by excessive catagen development.

Original languageEnglish (US)
Pages (from-to)221-234
Number of pages14
JournalAmerican Journal of Pathology
Volume168
Issue number1
DOIs
StatePublished - Jan 2006

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Peters, E. M. J., Stieglitz, M. G., Liezman, C., Overall, R. W., Nakamura, M., Hagen, E., Klapp, B. F., Arck, P., & Paus, R. (2006). p75 neurotrophin receptor-mediated signaling promotes human hair follicle regression (catagen). American Journal of Pathology, 168(1), 221-234. https://doi.org/10.2353/ajpath.2006.050163