Abstract
Neurotrophins exert many biological effects not directly targeted at neurons, including modulation of keratinocyte proliferation and apoptosis in vitro. Here we exploit the cyclic growth and regression activity of the murine hair follicle to explore potential nonneuronal functions of neurotrophins in the skin, and analyze the follicular expression and hair growth-modulatory function of BDNF, NT-4, and their high-affinity receptor, TrkB. The cutaneous expression of BDNF and NT-4 mRNA was strikingly hair cycle dependent and peaked during the spontaneous, apoptosis-driven hair follicle regression (catagen). During catagen, BDNF mRNA and immunoreactivity, as well as NT-4-immunoreactivity, were expressed in the regressing hair follicle compartments, whereas TrkB mRNA and immunoreactivity were seen in dermal papilla fibroblasts, epithelial strand, and hair germ. BDNF or NT-4 knockout mice showed significant catagen retardation, whereas BDNF-overexpressing mice displayed acceleration of catagen and significant shortening of hair length. Finally, BDNF and NT-4 accelerated catagen development in murine skin organ culture. Together, our data suggest that BDNF and NT-4 play a previously unrecognized role in skin physiology as agents of hair growth control. Thus, TrkB agonists and antagonists deserve exploration as novel hair growth-modulatory drugs for the management of common hair growth disorders.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 395-410 |
| Number of pages | 16 |
| Journal | FASEB Journal |
| Volume | 13 |
| Issue number | 2 |
| State | Published - Feb 16 1999 |
| Externally published | Yes |
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Keywords
- BDNF
- Catagen
- NT-4
- p75NTR
- TrkB
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
A new role for neurotrophins : Involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control. / Botchkarev, Vladimir A.; Botchkareva, Natalia V.; Welker, Pia; Metz, Martin; Lewin, Gary R.; Subramaniam, Arun; Bulfone-Paus, Silvia; Hagen, Evelin; Braun, Armin; Lommatzsch, Marek; Renz, Harald; Paus, Ralf.
In: FASEB Journal, Vol. 13, No. 2, 16.02.1999, p. 395-410.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A new role for neurotrophins
T2 - Involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control
AU - Botchkarev, Vladimir A.
AU - Botchkareva, Natalia V.
AU - Welker, Pia
AU - Metz, Martin
AU - Lewin, Gary R.
AU - Subramaniam, Arun
AU - Bulfone-Paus, Silvia
AU - Hagen, Evelin
AU - Braun, Armin
AU - Lommatzsch, Marek
AU - Renz, Harald
AU - Paus, Ralf
PY - 1999/2/16
Y1 - 1999/2/16
N2 - Neurotrophins exert many biological effects not directly targeted at neurons, including modulation of keratinocyte proliferation and apoptosis in vitro. Here we exploit the cyclic growth and regression activity of the murine hair follicle to explore potential nonneuronal functions of neurotrophins in the skin, and analyze the follicular expression and hair growth-modulatory function of BDNF, NT-4, and their high-affinity receptor, TrkB. The cutaneous expression of BDNF and NT-4 mRNA was strikingly hair cycle dependent and peaked during the spontaneous, apoptosis-driven hair follicle regression (catagen). During catagen, BDNF mRNA and immunoreactivity, as well as NT-4-immunoreactivity, were expressed in the regressing hair follicle compartments, whereas TrkB mRNA and immunoreactivity were seen in dermal papilla fibroblasts, epithelial strand, and hair germ. BDNF or NT-4 knockout mice showed significant catagen retardation, whereas BDNF-overexpressing mice displayed acceleration of catagen and significant shortening of hair length. Finally, BDNF and NT-4 accelerated catagen development in murine skin organ culture. Together, our data suggest that BDNF and NT-4 play a previously unrecognized role in skin physiology as agents of hair growth control. Thus, TrkB agonists and antagonists deserve exploration as novel hair growth-modulatory drugs for the management of common hair growth disorders.
AB - Neurotrophins exert many biological effects not directly targeted at neurons, including modulation of keratinocyte proliferation and apoptosis in vitro. Here we exploit the cyclic growth and regression activity of the murine hair follicle to explore potential nonneuronal functions of neurotrophins in the skin, and analyze the follicular expression and hair growth-modulatory function of BDNF, NT-4, and their high-affinity receptor, TrkB. The cutaneous expression of BDNF and NT-4 mRNA was strikingly hair cycle dependent and peaked during the spontaneous, apoptosis-driven hair follicle regression (catagen). During catagen, BDNF mRNA and immunoreactivity, as well as NT-4-immunoreactivity, were expressed in the regressing hair follicle compartments, whereas TrkB mRNA and immunoreactivity were seen in dermal papilla fibroblasts, epithelial strand, and hair germ. BDNF or NT-4 knockout mice showed significant catagen retardation, whereas BDNF-overexpressing mice displayed acceleration of catagen and significant shortening of hair length. Finally, BDNF and NT-4 accelerated catagen development in murine skin organ culture. Together, our data suggest that BDNF and NT-4 play a previously unrecognized role in skin physiology as agents of hair growth control. Thus, TrkB agonists and antagonists deserve exploration as novel hair growth-modulatory drugs for the management of common hair growth disorders.
KW - BDNF
KW - Catagen
KW - NT-4
KW - p75NTR
KW - TrkB
UR - http://www.scopus.com/inward/record.url?scp=0033005756&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033005756&partnerID=8YFLogxK
M3 - Article
C2 - 9973328
AN - SCOPUS:0033005756
VL - 13
SP - 395
EP - 410
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 2
ER -