Control of human hair growth by neurotrophins: brain-derived neurotrophic factor inhibits hair shaft elongation, induces catagen, and stimulates follicular transforming growth factor beta2 expression.
Neurotrophins are important modulators of epithelial-mesenchymal interactions. Previously, we had shown that brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tyrosine kinase B (TrkB) are prominently involved in the control of murine hair follicle cycling. We now show that BDNF and TrkB are also expressed in the human hair follicle in a manner that is both hair cycle dependent and suggestive of epithelial-mesenchymal cross-talk between BDNF-secreting dermal papilla fibroblasts of anagen hair follicles and subpopulations of TrkB+ hair follicle keratinocytes. As functional evidence for an involvement of BDNF/TrkB in human hair growth control, we show in organ-cultured human anagen hair follicles that 50 ng per mL BDNF significantly inhibit hair shaft elongation, induce premature catagen development, and inhibit keratinocyte proliferation. Quantitative real-time rtPCR analysis demonstrates upregulation of the potent catagen inducer, transforming growth factor beta2 (TGFbeta2) by BDNF, whereas catagen induction by BDNF was partially reversible through co-administration of TGFbeta-neutralizing antibody. This suggests that TrkB-mediated signaling promotes the switch between anagen and catagen at least in part via upregulation of TGFbeta2. Thus, human scalp hair follicles are both a source and target of bioregulation by BDNF, which invites to target TrkB-mediated signaling for therapeutic hair growth modulation.
Peters
Eva M J
EM
Department of Internal Medicine, Biomedical Research Center, University Medicine Charité, Campus Virchow Hospital, Berlin, Germany. frl_peters@yahoo.com
Hansen
Marit G
MG
Overall
Rupert W
RW
Nakamura
Motonobu
M
Pertile
Paolo
P
Klapp
Burghard F
BF
Arck
Petra C
PC
Paus
Ralf
R
D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053781:Transforming Growth Factor beta2; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D011994:Recombinant Proteins; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D020813:Receptor, trkB