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Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.


ABSTRACT:

Background

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 GSK3? inhibitor that activates the Wnt/?-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/?-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/?-catenin pathway. VPA analogs and other GSK3? inhibitors that activate the Wnt/?-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/?-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.

SUBMITTER: Lee SH 

PROVIDER: S-EPMC3323655 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.

Lee Soung-Hoon SH   Yoon Juyong J   Shin Seung Ho SH   Zahoor Muhamad M   Kim Hyoung Jun HJ   Park Phil June PJ   Park Won-Seok WS   Min Do Sik do S   Kim Hyun-Yi HY   Choi Kang-Yell KY  

PloS one 20120410 4


<h4>Background</h4>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.<h4>Methodology/ principal findings</h4>Topical application of VPA to male C3H mice critically stimulated hair re-growth a  ...[more]

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