P5.51 the cutaneous vanilloid receptor-1 (VR1) is involved in human hair growth control

Bodó E.^1,3, Bíró T.¹, Telek A.¹, Czifra G.¹, Griger Z.¹, Tóth I.B.¹, Lázár J.¹, Meschalchin A.², Ito T.³, Bettermann A.³, Pertile P.², Kovács L.¹, and Paus R.³

¹Dept. of Physiology, University of Debrecen, Hungary; ²Cutech Srl, Padova, Italy; ³Dept. of Dermatology, University of Hamburg, Germany

Objectives: To describe the expression of vanilloid receptor 1 (VR1), a key molecular integrator of nociceptive mechanisms of sensory neurons, in human skin and to investigate its role in regulating functions of the human hair follicle (HF), as a prototypic epithelial-mesenchymal interaction system.

Methods: Immunohistochemistry and PCR-based techniques (Q-PCR, Micro Array) were used to identify VR1 and various markers of HF biology, whereas functional assays (growth curve analysis, proliferation ELISA, calcium imaging, flow cytometry) were applied to detect VR1-mediated cellular processes.

Results: In normal human skin, a strong VR1 immunoreactivity (VR1-ir) was identified on basal (but not suprabasal) keratinocytes and Langerhans cells of the epidermis, on skin nerve fibres, on sebocytes and sweat gland epithelium, endothelial and smooth muscle cells of skin blood vessels, and on mast cells. No VR1 immunoreactivity was observed on melanocytes and fibroblasts. In the HF (both organ cultured and in situ), VR1-ir was confined to distinct epithelial compartments of HF in anagen and catagen but not to dermal papilla fibroblasts and HF melanocytes. In organ culture, VR1 activation by capsaicin resulted in a dose-dependent and VR1-specific inhibition of hair shaft elongation, suppression of proliferation, promotion of apoptosis, and induction of catagen transformation, possibly due to up-regulation of a potent hair growth inhibitor TGFb₂. Cultured outer root sheath (ORS) keratinocytes also expressed functional VR1, whose stimulation inhibited proliferation, induced apoptosis, and elevated intracellular calcium concentration. Finally, VR1 stimulation of ORS keratinocytes up-regulated the expression of recognized endogenous hair growth inhibitors (IL-1b, TGFb₂) and down-regulated the expression of stimulators (HGF, IGF-1, SCF), while key differentiation markers (CK17, CK14, filaggrin, involucrin) remained unaffected.

Conclusion: VR1 is a significant novel player in human hair growth control underscoring that its physiological functions in human skin extend far beyond sensory neuron-coupled nociception.