Activation of thermoTRPV3 channels accounts for abnormal hair growth by natural skin sensitizer carvacrol
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, understanding the cause of dysfunctional hair follicles is critical to prevention of hair loss or alleviating dermatologic or systemic diseases with hair abnormalities. The outer root sheath (ORS) cells of human hair follicles are fundamental for maintaining the intact structure of hair follicles and regulating hair growth. We found that pharmacological activation of cutaneous warm-temperature sensitive and Ca2+ permeable TRPV3 channels expressed in the ORS cells by natural skin sensitizer carvacrol increased the apoptosis of human ORS cells. Silencing of TRPV3 by short-hairpin RNA reversed the cell death of human ORS cells induced by carvacrol. Activation of TRPV3 by agonist carvacrol inhibited the hair growth and also reduced the number of hair follicles on the back of mice. Conversely, we have identified a natural compound forsythoside B that selectively inhibited TRPV3 and attenuated apoptosis in ORS cells. Forsythoside B also increased the hair follicles counts and promote the normal hair growth. Taken together, our findings show that cutaneous TRPV3 channel function is critical for regulation of hair growth, and inhibition of overactive TRPV3 may represent a promising therapy for hair loss or hair follicle–related skin diseases.