Title: The Role of Transient Receptor Potential Vanilloid 4 (TRPV4) in Regulating Murine Hair Growth and Follicle Density

Introduction: Hair growth is a highly regulated physiological process characterized by cyclical phases of active growth (anagen), regression (catagen), and rest (telogen). Fundamental to this morphogenesis is calcium signaling, which modulates the release of essential growth factors such as TGF-alpha and EGFR. While other members of the transient receptor potential (TRP) family, such as TRPV1 and TRPV3, have established roles in hair cycle regulation, the specific contribution of the calcium-permeable cation channel TRPV4—expressed widely in skin keratinocytes—remains largely uncharacterized.

Aims/Objectives: The primary objective of this study was to investigate the physiological impact of TRPV4 deletion on hair regrowth in a murine model. Specific aims included: 1) Evaluating the progression of hair regrowth via digital analysis; 2) Quantifying growth parameters, including hair length ratio and weekly growth rates; and 3) Conducting histological assessments to compare hair follicle density between wild-type (WT) and TRPV4 knockout (TRPV4KO) mice.

Methods: All experimental procedures were conducted in accordance with institutional ethical standards for animal care at Qatar University and Sultan Qaboos University. Male C57BL/6NCr (WT) and TRPV4KO mice (9–11 weeks old; n=4 per group based on representative visual data) were used. Under anesthesia, the back and abdominal regions were shaved and treated with hair removal cream. Hair regrowth was monitored weekly for four weeks through digital photography. Three hairs were collected per week from each region to calculate the average length, length ratio, and growth rate. At week 4, skin biopsies were obtained, stained with Hematoxylin and Eosin (H&E), and scanned to quantify hair follicle density within a 1.2 cm area. Statistical analysis was performed using t-tests, with data presented as mean ± SEM.

Results: Visual assessment confirmed that hair regrowth was markedly delayed in TRPV4KO mice compared to WT. In the back region, TRPV4KO mice exhibited a significantly lower hair length ratio at week 1 (p < 0.05) and week 2 (p < 0.001). Similarly, the back hair growth rate was significantly reduced in KO mice during week 1 (p < 0.05) and week 2 (p < 0.001). Histological analysis at week 4 revealed that TRPV4KO mice had significantly fewer hair follicles in the back region compared to WT (p < 0.05). Conversely, the abdominal region showed more resilience, with significant decreases in growth rate appearing only by week 4 (p < 0.05), while the hair length ratio showed no significant difference throughout the study.

Conclusions: These findings demonstrate that TRPV4 is a positive regulator of hair growth in mice. Its deletion results in a significant delay in the hair growth cycle and a reduction in follicle density, likely due to impaired calcium signaling affecting the proliferation of matrix cells. The regional variations observed suggest that TRPV4 influence may depend on the specific physiological environment of the follicles. Consequently, TRPV4 represents a potential therapeutic target for the management of hair loss and growth disorders.