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

Abstract

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, 10-1,000 μM) or synthetic (e.g., 2-aminoethoxydiphenyl borate, 1-300 μM) 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.

TRP Channels and Pruritus

“…Keratinocytes from these animals showed a highly augmented Ca 2+ elevation in response to thermal stimulation and histological analysis of the skin revealed the inhibition of hair follicle growth [299]. In line with these findings, activation of TRPV3 was also found to be a negative regulator of the human hair cycle [300]. Transgenic mice overexpressing the above gene-of-function mutation in the epidermal keratinocytes also exhibited symptoms of severe itch, AD-like dermatitis, and increased serum levels of IgE and various proinflammatory cytokines.…”

Intracellular Proton-mediated Activation of TRPV3 Channels Accounts for the Exfoliation Effect of α-Hydroxyl Acids on Keratinocytes

“…These results are consistent with the idea that glycolic acid induces cell damage by activating TRPV3. In addition, we tested the effect of TRPV3 (56) as well as the report that TRPV3 activation induces cell death in human outer root sheath keratinocytes (27).…”

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

“…SZ95 sebocytes were treated for 1 hour with vehicle or CBD (10 μM). Cells were then lysed (cell density: 10 7 cells per ml), and lysates were assayed immediately according to the manufacturer's protocol, using Parameter Cyclic AMP Assay (R&D Systems ] IC were determined following 1 μM Fluo-4 AM loading by Fluorescent Image Plate Reader, as described in our previous report (80).…”