Pharmacological activation of thermoTRPV3 channels inhibits hair growth by inducing cell death of hair follicle outer root sheath.

J Pharmacol Exp Ther. 2019 May 31. pii: jpet.119.258087. doi: 10.1124/jpet.119.258087. [Epub ahead of print]
Pharmacological activation of thermoTRPV3 channels inhibits hair growth by inducing cell death of hair follicle outer root sheath.
Yan K1, Sun X1, Wang G1, Liu Y2, Wang K3.

Hair growth starts from hair follicles that reside in dermis, and abnormal hair growth is an early sign of hair follicle disease or systemic illness such as alopecia or hair loss. Therefore, identifying a target critical for dysfunctional hair follicles is fundamental to alleviating dermatologic or systemic diseases with hair abnormalities. The warm temperature-activated Ca2+-permeable TRPV3 channel protein is abundantly expressed in the skin keratinocytes, and dysfunctional TRPV3 causes human congenital Olmsted syndrome characterized by skin diseases and alopecia, indicating an important role of TRPV3 in hair follicle development and hair growth. To validate TRPV3 as a therapeutic target, we investigated the impact of pharmacological modulation of TRPV3 on hair growth using a combination of biochemical and cell biology, immunohistochemical, whole-cell patch clamp, RNA interference and pharmacological approaches. We find that functional TRPV3 channel proteins are highly expressed in hair follicle outer root sheath (ORS) cells as detected by Western blot analysis, immunohistochemical staining and electrophysiological techniques. Pharmacological activation of TRPV3 by agonist natural carvacrol induces cell death of ORS cells and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Conversely, specific inhibition of TRPV3 by inhibitor natural forsythoside B (FB) and shRNA reverses the cell death induced by carvacrol-mediated TRPV3 activation in human ORS cells. Furthermore, forsythoside B results in a significant reversal of hair growth inhibition induced by agonist carvacrol. Altogether, our findings demonstrate that TRPV3 channel is critical for regulation of hair growth, and inhibition of TRPV3 may represent a promising therapy for hair loss or hair follicle-related skin diseases.

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http://jpet.aspetjournals.org/content/jpet/early/2019/05/31/jpet.119.258087.full.pdf