Transient stimulation of TRPV4-expressing keratinocytes promotes hair follicle regeneration in mice
Pu Yang 1, Ping Lu 1 2, Jialie Luo 1, Lixia Du 1, Jing Feng 1, Tao Cai 1 3, Yi Yuan 1, Hunter Cheng 1, Hongzhen Hu 1
1Department of Anesthesiology, The Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, Missouri, USA
2Experimental Research Center, Dermatology Hospital, Southern Medical University, Guangzhou, China
3Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Background and Purpose: 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 regenera- tion in vivo remains incompletely understood.
Experimental Approach: 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 regenera- tion. Chemical cues and signal molecules involved in hair follicle cycle progression were measured by immunofluorescence staining, quantitative RT-PCR and western blotting.
Key Results: 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.
Conclusion and Implications: 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.
