Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.
Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.
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DOI：
10.1371/journal.pone.0034152
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Choi KY
中科院分区：
文献类型：
--
作者：
Lee SH;Yoon J;Shin SH;Zahoor M;Kim HJ;Park PJ;Park WS;Min do S;Kim HY;Choi KY
脱发是一种常见的脱发问题，会影响很多人。然而，目前治疗脱发的方法受到低疗效和潜在不良副作用的限制。我们已经确定了丙戊酸（VPA）的新功能，它是一种激活Wnt/β-catenin通路的GSK3β抑制剂，在体外和体内促进头发再生。局部应用VPA刺激雄性C3H小鼠毛发再生，诱导终分化表皮标记物如聚丝蛋白和loricrin，以及真皮乳头标记物碱性磷酸酶（ALP）。VPA通过上调Wnt/β-catenin通路诱导人真皮乳头细胞ALP，而治疗脱发的常用药物米诺地尔（minoxidil， MNX）对Wnt/β-catenin通路无显著影响。VPA类似物和其他激活Wnt/β-catenin通路的GSK3β抑制剂，如4-苯基丁酸、LiCl和BeCl2，在体内也表现出促进头发生长的活性。重要的是，VPA，而不是MNX，成功地刺激了C3H小鼠伤口中的毛发生长。我们的研究结果表明，激活Wnt/β-catenin通路的小分子，如VPA，可能被开发成刺激头发再生的药物。
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. 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 BeCl2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice. 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.
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影响因子：
2.5
作者：
Iida, Machiko;Ihara, Setsunosuke;Matsuzaki, Takashi
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0505259102
发表时间：
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影响因子：
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作者：
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