Hair growth-promoting effect of recombinant human sonic hedgehog proteins

[摘要] Hair loss, known as alopecia, causes psychological stress and influences social interactions. At present, treatment for hair loss is somewhat limited, transient, and unpredictable. Based on the critical role of sonic hedgehog (Shh) in hair follicle development, Shh itself would be a good therapeutic candidate for the prevention of hair loss as well as promotion of hair growth. To investigate its potential use for hair treatment, we overexpressed Shh protein in E.coli by making silent mutations in 12 amino acids from N-terminus of Shh and purified it with Ni-affinity chromatography. Purified Shh proteins were able to activate Gli-responsive luciferase reporter gene in a dose-dependent manner and induce the alkaline phosphatase (AP) activity in the presence of bone morphogenic protein 4 (BMP-4). In addition, we confirmed that the treatment of recombinant Shh proteins to human dermal papilla (hDP) cells significantly increased the expressions of Shh-responsive genes as well as hair growth-related genes. Finally, we found that the administration of Shh proteins into the dorsal skin of the mouse could promote the hair density and length. Exogenous Shh proteins induced hair-related gene expression by stimulating both Shh signaling pathway and Wnt/β-catenin pathway in DP cells, and might therefore be a potential hair promoting agent.

[学科分类] 皮肤病学

[关键词] Recombinant sonic hedgehog;Random mutation;Hair growth;human dermal papilla