Transient stimulation of TRPV4-expressing keratinocytes promotes hair follicle regeneration in mice.

Abstract

Hair follicle telogen to anagen transition results in a break in cellular quiescence of the hair follicle stem cells, which subsequently promotes hair follicle regeneration. Many critical molecules and signalling pathways are involved in hair follicle cycle progression. Transient receptor potential vanilloid 4 (TRPV4) is a polymodal sensory transducer that regulates various cutaneous functions under both normal and disease conditions. However, the role of TRPV4 in hair follicle regeneration in vivo remains incompletely understood. Using adult C57BL/6J mice, keratinocyte (K14Cre ; Trpv4f/f ) and macrophage (Cx3cr1Cre ; Trpv4f/f ) Trpv4 conditional knockout (cKO) mice, Trpv4-/- mice, we investigated the effect of a single intradermal injection of GSK1016790A, a potent and selective small molecule TRPV4 activator, on hair follicle regeneration. Chemical cues and signal molecules involved in hair follicle cycle progression were measured by immunofluorescence staining, quantitative RT-PCR and western blotting. Here, we show that a single intradermal injection of GSK1016790A is sufficient to induce telogen to anagen transition and hair follicle regeneration in mice by increasing the expression of the anagen-promoting growth factors and down-regulating the expression of growth factors that inhibit anagen. The action of GSK1016790A relies largely on the function of TRPV4 in skin and involves activation of downstream ERK signalling. Our results suggest that transient chemical activation of TRPV4 in the skin induces hair follicle regeneration in mice, which might provide an effective therapeutic strategy for the treatment of hair loss and alopecia.