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Activation of Transient Receptor Potential Vanilloid-3 Inhibits Human Hair Growth

2011; Elsevier BV; Volume: 131; Issue: 8 Linguagem: Inglês

10.1038/jid.2011.122

1523-1747

István Borbíró, Erika Lisztes, Balázs I. Tóth, Gabriella Czifra, Attila Oláh, Attila Gábor Szöllősi, Norbert Szentandrássy, Péter P. Nánási, Zoltán Péter, Ralf Paus, László Kovács, Tamás Bı́ró,

Pharmacological Effects of Natural Compounds

In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human hair growth. TRPV3 immunoreactivity was confined to epithelial compartments of the human HF, mainly to the ORS. In organ culture, TRPV3 activation by plant-derived (e.g., eugenol, 10–1,000μM) or synthetic (e.g., 2-aminoethoxydiphenyl borate, 1–300μM) agonists resulted in a dose-dependent inhibition of hair shaft elongation, suppression of proliferation, and induction of apoptosis and premature HF regression (catagen). Human ORS keratinocytes also expressed functional TRPV3, whose stimulation induced membrane currents, elevated intracellular calcium concentration, inhibited proliferation, and induced apoptosis. Of great importance, these effects on ORS keratinocytes were all mediated by TRPV3, as small interfering RNA-mediated silencing of TRPV3 effectively abrogated the cellular actions of the above agonists. These findings collectively support the concept that TRPV3 signaling is a significant player in human hair growth control. Therefore, TRPV3 and the related intracellular signaling mechanism might function as a promising target for pharmacological manipulations of clinically relevant hair growth disorders. In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human hair growth. TRPV3 immunoreactivity was confined to epithelial compartments of the human HF, mainly to the ORS. In organ culture, TRPV3 activation by plant-derived (e.g., eugenol, 10–1,000μM) or synthetic (e.g., 2-aminoethoxydiphenyl borate, 1–300μM) agonists resulted in a dose-dependent inhibition of hair shaft elongation, suppression of proliferation, and induction of apoptosis and premature HF regression (catagen). Human ORS keratinocytes also expressed functional TRPV3, whose stimulation induced membrane currents, elevated intracellular calcium concentration, inhibited proliferation, and induced apoptosis. Of great importance, these effects on ORS keratinocytes were all mediated by TRPV3, as small interfering RNA-mediated silencing of TRPV3 effectively abrogated the cellular actions of the above agonists. These findings collectively support the concept that TRPV3 signaling is a significant player in human hair growth control. Therefore, TRPV3 and the related intracellular signaling mechanism might function as a promising target for pharmacological manipulations of clinically relevant hair growth disorders. 2-aminoethoxydiphenyl borate human dermal fibroblast hair follicle immunoreactivity outer root sheath RNA interference transient receptor potential transient receptor potential vanilloid-3