Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
PLoS One. 2012;7(4):e34152. doi: 10.1371/journal.pone.0034152. Epub 2012 Apr 10.
Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo.
METHODOLOGY/ PRINCIPAL FINDINGS: Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2) also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice.
CONCLUSIONS/ SIGNIFICANCE: Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.
脱发是一种常见的毛发问题，可能会影响很多人。然而，目前治疗脱发的方法疗效有限，且可能存在不良反应。我们发现丙戊酸（VPA）具有一种新的功能，即作为一种 GSK3β 抑制剂激活 Wnt/β-catenin 通路，从而促进体外和体内的毛发生长。
方法/主要发现：将 VPA 局部应用于雄性 C3H 小鼠，可显著刺激毛发生长，并诱导终末分化的表皮标志物，如丝聚合蛋白和兜甲蛋白，以及真皮乳头标志物碱性磷酸酶（ALP）。VPA 通过上调 Wnt/β-catenin 通路诱导人真皮乳头细胞中的 ALP，而米诺地尔（MNX）是一种常用于治疗脱发的药物，对 Wnt/β-catenin 通路没有显著影响。激活 Wnt/β-catenin 通路的 VPA 类似物和其他 GSK3β 抑制剂，如 4-苯丁酸、LiCl 和 BeCl2，在体内也表现出促进毛发生长的活性。重要的是，VPA 而不是 MNX，成功地刺激了 C3H 小鼠伤口处的毛发生长。
结论/意义：我们的研究结果表明，激活 Wnt/β-catenin 通路的小分子，如 VPA，有可能被开发成刺激毛发生长的药物。
