Fisetin Promotes Hair Growth by Augmenting TERT Expression.
Fisetin Promotes Hair Growth by Augmenting TERT Expression.
复制标题
DOI：
10.3389/fcell.2020.566617
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Katakura Y
中科院分区：
文献类型：
--
作者：
Kubo C;Ogawa M;Uehara N;Katakura Y
尽管头发稀疏和脱发不被认为是严重疾病，但脱发会对心理健康和生活质量产生影响；因此，已经进行了大量的研究来开发新型毛发生长剂。在本研究中，我们旨在研究端粒酶逆转录酶（TERT）的潜力，因为皮肤中TERT的过度表达会激活静息毛囊膨出干细胞，从而触发新毛囊生长期的启动并促进毛发合成。为此，我们筛选了可激活角质形成细胞中 TERT 表达的多酚，并鉴定出白藜芦醇和非瑟酮是强 hTERT 增强化合物。这些多酚还调节细胞因子的基因表达，例如IGF-1和KGF，激活β-连环蛋白途径，以及TGF-β1，在维持毛囊干细胞的生态位中发挥重要作用，因此被认为在促进头发生长方面发挥作用。我们还表明，这些多酚，尤其是非瑟酮，促进了剃毛的小鼠背部皮肤的毛发生长，这表明这些多酚激活了从休止期到毛发生长初期的转变。组织学研究表明，用这些多酚治疗的小鼠的背部皮肤含有大量毛囊，并且与对照小鼠相比变厚。此外，在用白藜芦醇和非瑟酮处理的小鼠背部皮肤上，在毛乳头周围观察到许多增殖细胞（Ki67+细胞）。这些结果表明，白藜芦醇和非瑟酮通过诱导毛囊隆起干细胞增殖，诱导毛囊从休止期向毛发生长初期转变，从而促进毛发生长。
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.