Neurotrophin-3 Involvement in the Regulation of Hair Follicle Morphogenesis

Botchkarev, Vladimir A.; Botchkareva, Natalia V.; Albers, Kathryn M.; Veen, Carina van der; Lewin, Gary R.; Paus, Ralf

doi:10.1046/j.1523-1747.1998.00277.x

Cited by 87 publications

(165 citation statements)

References 79 publications

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“…Further, NGF can significantly enhance the percentage of hair follicles in advanced catagen stages. 27,28,50 This is in line with our present in vivo observations of premature catagen development in stressed mice, where levels of NGF are up-regulated.…”

Section: Discussionsupporting

confidence: 91%

“…Botchkarev et al 27 and others previously reported that NGF is detectable in the skin, along with the other members of the NT family. Further, NGF can significantly enhance the percentage of hair follicles in advanced catagen stages.…”

Section: Discussionmentioning

confidence: 90%

“…27 Briefly, the sections were washed with Tris-buffered saline solution (TBS, pH ϭ 7.4) for 15 minutes and blocked with 2% normal goat serum (Dako) diluted in TBS for 30 minutes at room temperature (RT) to reduce non-specific binding. The cryosections were then incubated overnight at RT in a humidity chamber with the corresponding primary antibody at a dilution of 1:50 for NGF (Santra Cruz), 1:100 for TrkA (Santra Cruz) and 1:100 for p75NTR (Chemicon, Hofheim, Germany).…”

Section: Fluorescence Immunohistochemistry For Skin Tissuementioning

confidence: 99%

“…24 The presence of NGF in murine skin has recently been described, 25,26 alluding to its involvement in the control of apoptosis-driven hair follicle regression (catagen). [27][28][29] Specifically, selected NTs accelerate catagen most likely by stimulating the p75NTR receptor, which is expressed in the regressing outer root sheath (ORS) and is known to mediate apoptosis when activated alone. 27,30 -32 Based on these recent insights into the role of NTs in hair growth control and the central role of NGF in stressinduced neurogenic inflammation, we hypothesized that NGF production in the skin is up-regulated following stress exposure, which in turn promotes up-regulation and release of neuropeptides, eg, SP from sensory cfibers.…”

mentioning

confidence: 99%

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Neurogenic Inflammation in Stress-Induced Termination of Murine Hair Growth Is Promoted by Nerve Growth Factor

Peters

Handjiski

Kuhlmei

et al. 2004

The American Journal of Pathology

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114

161

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Recently, we have revealed the existence of a "brainhair follicle axis" in murine skin and have identified the neuropeptide substance P (SP) as a key mediator of stress-induced hair growth inhibition in vivo. Published evidence suggests that increased numbers of SP-immunoreactive sensory fibers, as seen in the dermis of stressed mice in anagen-catagen transition, are a result of transient high levels of nerve growth factor (NGF). Thus, we now aimed at dissecting the role of NGF in stress-triggered hair growth termination in our murine model. By real time PCR and immunohistochemistry, stress-exposed mice showed an up-regulation of NGF and its low-affinity receptor p75NTR; the NGF high-affinity receptor TrkA was moderately down-regulated. On neutralization of NGF, premature onset of catagen, apoptosis, and increased number/ activation of perifollicular mast cells and antigen-presenting cells, which reflects the skin response to stress, was significantly abrogated. Stress or subcutaneous injection of recombinant NGF (to mimic stress) resulted in an increased percentage of SP ؉ neurons in dorsal root ganglia, as measured by retrograde tracing. Taken together, these data suggest that NGF is a central element in the perifollicular neurogenic inflammation that develops during the murine skin response to stress and antagonizing NGF may be a promising therapeutic approach to counter the negative effect of stress on hair growth. Recently, we have introduced a mouse model launching experimental evidence that stress-induced hair loss is fact, and not fiction, as every so often imputed by a number of dermatologists. This mouse model provides new insights into the pathophysiology of stress-induced hair growth inhibition and permits exploration of various strategies for therapeutic intervention. 1,2 In this model, exposure to sonic stress inhibits the growth of a hair shaft producing (anagen) hair follicle by premature induction of hair follicle regression (catagen) and up-regulated keratinocyte apoptosis. At the same time, it induces neurogenic inflammation characterized by perifollicular mast cell degranulation and accumulation of antigen-presenting cells, eg, activated macrophages. 3 The neuropeptide substance P (SP) was identified as a key mediator of stress-induced hair growth inhibition, since increased number of SP-immunreactive nerve fibers were present in the skin of stressed mice and hair growth inhibition could be blocked by SP-receptor antagonists.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 90%

Section: Fluorescence Immunohistochemistry For Skin Tissuementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Neurogenic Inflammation in Stress-Induced Termination of Murine Hair Growth Is Promoted by Nerve Growth Factor

Peters

Handjiski

Kuhlmei

et al. 2004

The American Journal of Pathology

Self Cite

114

161

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show abstract

“…We can exclude NT-3 as a neuronderived trophic factor, as we find high levels of NT-3 in Merkel cells themselves and in neighboring epithelial cells in the outer root sheath. This notion is in agreement with the observation of epidermal NT-3 immunoreactivity by Schecterson and Bothwell (1992), Farinas et al (1996), and Botchkarev et al (1998). Furthermore, neuron-derived NT-3 is not available to postnatal Merkel cells as dorsal root ganglion neurons no longer express NT-3 after E16 (Schecterson and Bothwell, 1992).…”

Section: Discussionsupporting

confidence: 91%