Abstract
Although thinning hair and alopecia are not recognized as severe diseases, hair loss has implications for mental health and quality of life; therefore, a large number of studies have been carried out to develop novel hair growth agents. In the present study, we aimed to examine the potential of telomerase reverse transcriptase (TERT), because TERT overexpression in skin activates resting hair follicle bulge stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To this end, we screened polyphenols that activate TERT expression in keratinocytes, and identified resveratrol and fisetin as strong hTERT-augmenting compounds. These polyphenols also regulated the gene expression of cytokines such as IGF-1 and KGF, which activate the β-catenin pathway, and TGF-β1, which plays an important role in maintaining the niche of hair follicle stem cells, thus are thought to play roles in promoting hair growth. We additionally showed that these polyphenols, especially fisetin, promoted hair growth from the shaved dorsal skin of mice, which suggests that these polyphenols activate the transition from telogen to anagen phase. Histological studies indicated that the dorsal skin of mice treated with these polyphenols contained numerous hair follicles and was thickened compared with that in control mice. Furthermore, on the dorsal skin of mice treated with resveratrol and fisetin, a number of proliferating cells (Ki67+ cells) were observed around the hair papilla. These results suggest that resveratrol and fisetin induce a shift from telogen to anagen in the hair follicle by inducing proliferation of hair follicle bulge stem cells, thus promoting hair growth.
Highlights
Various methods for the treatment of hair thinning and alopecia have been developed
We found that the polyphenols, except eugeniin, augmented the expression of human TERT (hTERT) in HaCaT cells (Figure 1B)
On the dorsal skin of mice treated with resveratrol (Figure 9B) and fisetin (Figure 9C), and nontreated mice (Figure 9A), a number of proliferating cells (Ki67+ cells, arrow head) were observed around hair matrix and around outer/inner root sheath (ORS/IRS). These results indicate that hTERT induction in the epidermis triggers the proliferation of cells such as hair follicle dermal papilla, hair matrix cells and ORS/IRS, which results in the formation of hair follicle and promotion of hair growth in mice treated with hTERTaugmenting polyphenols
Summary
Various methods for the treatment of hair thinning and alopecia have been developed. The use of medicinal compounds has been shown to drastically improve hair growth. Two well-known compounds, finasteride and minoxidil, are used to improve thin hair and alopecia. Finasteride, a synthetic 5-α-reductase inhibitor, is used to treat alopecia by suppressing male hormones, but is reported to cause sexual dysfunction (Shen et al, 2018). Minoxidil was originally used as an antihypertensive medication, but is used as a topical formulation for promoting hair growth. The precise mechanisms of action of minoxidil are not fully understood (Suchonwanit et al, 2019). In this study, we focused on telomerase reverse transcriptase (TERT) as a novel target for the induction of hair growth
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