title: A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control.
abstract: The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory neurons as a central integrator of various nociceptive stimuli. However, several human skin cell populations are also now recognized to express TRPV1, but with unknown function. Exploiting the human hair follicle (HF) as a prototypic epithelial-mesenchymal interaction system, we have characterized the HF expression of TRPV1 in situ and have examined TRPV1 signaling in organ-cultured human scalp HF and outer root sheath (ORS) keratinocytes in vitro. TRPV1 immunoreactivity was confined to distinct epithelial compartments of the human HF, mainly to the ORS and hair matrix. In organ culture, TRPV1 activation by capsaicin resulted in a dose-dependent and TRPV1-specific inhibition of hair shaft elongation, suppression of proliferation, induction of apoptosis, premature HF regression (catagen), and up-regulation of intrafollicular transforming growth factor-beta(2). Cultured human ORS keratinocytes also expressed functional TRPV1, whose stimulation inhibited proliferation, induced apoptosis, elevated intracellular calcium concentration, up-regulated known endogenous hair growth inhibitors (interleukin-1beta, transforming growth factor-beta(2)), and down-regulated known hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor). These findings strongly support TRPV1 as a significant novel player in human hair growth control, underscore the physiological importance of TRPV1 in human skin beyond nociception, and identify TRPV1 as a promising, novel target for pharmacological manipulations of epithelial growth disorders.
authors.affiliation: Department of Physiology, University of Debrecen, MHSC, 4012 Debrecen, Nagyerdei krt. 98., Hungary.
authors.forename: Eniko
authors.initials: E
authors.lastname: Bodó
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.forename: Andrea
authors.initials: A
authors.lastname: Telek
authors.forename: Gabriella
authors.initials: G
authors.lastname: Czifra
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Griger
authors.forename: Balázs I
authors.initials: BI
authors.lastname: Tóth
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mescalchin
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bettermann
authors.forename: László
authors.initials: L
authors.lastname: Kovács
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006133:Growth Substances / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D011955:Receptors, Drug / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D006133:Growth Substances; D011955:Receptors, Drug; D002211:Capsaicin