TRPV4 Activation Promotes Hair Growth via TSLP Signaling in the Skin

Hair follicle cycling is regulated by complex signaling networks that coordinate stem cell activation and quiescence. Although transient receptor potential vanilloid 4 (TRPV4) is expressed in the skin and implicated in cutaneous physiology, its role in hair growth remains unclear. Here, we investigated the contribution of TRPV4 activation to hair growth and its relationship with thymic stromal lymphopoietin (TSLP). Pharmacological activation of TRPV4 using GSK1016790A significantly promoted hair regrowth and elongation in mice, whereas TRPV4 inhibition attenuated these effects. Consistently, Trpv4⁻^/⁻ mice exhibited spontaneous hair loss, supporting a role for TRPV4 in maintaining hair homeostasis. TRPV4 activation increased TSLP production in the skin, and exogenous TSLP recapitulated the pro-growth effects of TRPV4 activation. These effects were suppressed by pharmacological blockade of the TSLP receptor, indicating TSLP-dependent signaling. Notably, TSLP restored hair growth in Trpv4⁻^/⁻ mice, whereas TRPV4 activation did not, supporting the notion that TSLP acts downstream of TRPV4. In contrast, activation of TRPV3, another TRP channel abundantly expressed in the skin, did not significantly affect hair growth, highlighting the specific role of TRPV4 in this process. Overall, these findings identify a TRPV4-TSLP signaling axis that promotes hair growth and regulates hair follicle function, suggesting a potential therapeutic target for hair loss disorders.