014 Growth Factor Secretion by Dermal Papilla Cells is Regulated by Neurotrophins

DJ Tobin1, VA Botchkarev2, P Welker3, NV Botchkareva2, and R Paus4. Dept. of Biomedical Sciences, University of Bradford, Bradford, England1, Dept. of Dermatology, Boston University School of Medicine, Boston, USA2; Dept. of Dermatology, University Hospital Eppendorf, Hamburg, Germany4; and Dept. of Dermatology, Charité, Humboldt-University Berlin, Germany3.

Neurotrophins have several non-neuronal functions in the skin. Previously we have shown that p75 kD neurotrophin receptor plays an important role during HF morphogenesis and that neurotrophins (NT) accelerate hair follicle (HF) regression (catagen), most likely by stimulating keratinocyte apoptosis via binding to the p75 kD neurotrophin receptor. In addition, dermal papilla (DP) cells express high affinity NT receptors TrkB and TrkC during the HF anagen-catagen transition. Given that the DP is inductive during hair follicle morphogenesis and cycling, NT may contribute to the regulation of this mesenchymal cell population by modulating their growth factor secretion. To test this hypothesis, matched cultures of human scalp DP cells and dermal fibroblasts (n=6) were grown in the presence of 0.5-50 ng/ml of NGF, BDNF, NT-3 or NT-4. Secretion of different growth factors (SCF, VEGF, TGFb2, KGF) known to be produced by DP cells during anagen was assessed after 48 h by ELISA. Both DP cells and dermal fibroblasts were found to express TrkA, TrkC, and p75 kD neurotrophin receptors by immunohistochemistry. TrkB receptors however, were detected on DP cells but not on dermal fibroblasts. The NT tested had no significant effect on DP cell or dermal fibroblast proliferation. By ELISA, secretion of SCF by DP cells into supernatants was significantly down regulated by BDNF and NT-3, while VEGF secretion was decreased after NT-4 treatment. BDNF also significantly decreased TGFß2 secretion by DP cells. Interestingly, the secretion of these growth factors by dermal fibroblasts was not affected by NT, suggesting that in addition to TrkB expression on DP, but not dermal fibroblasts, this secretary response to NT may aid the discrimination of interfollicular dermal fibroblasts from DP fibroblasts. These data suggest that NT may modulate HF cycling by altering secretion of DP-derived growth factors that control proliferation, apoptosis and/or differentiation of hair matrix cells.