l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase

Summary Background l‐Ascorbic acid 2‐phosphate (Asc 2‐P), a derivative of l‐ascorbic acid, promotes elongation of hair shafts in cultured human hair follicles and induces hair growth in mice. Objectives To investigate whether the promotion of hair growth by Asc 2‐P is mediated by insulin‐like growth factor‐1 (IGF‐1) and, if so, to investigate the mechanism of the Asc 2‐P‐induced IGF‐1 expression. Methods Dermal papilla (DP) cells were cultured and IGF‐1 level was measured by reverse transcription–polymerase chain reaction and enzyme‐linked immunosorbent assay after Asc 2‐P treatment in the absence or presence of LY294002, a phosphatidylinositol 3‐kinase (PI3K) inhibitor. Also, hair shaft elongation in cultured human scalp hair follicles and proliferation of cocultured keratinocytes were examined after Asc 2‐P treatment in the absence or presence of neutralizing antibody against IGF‐1. In addition, keratinocyte proliferation in cultured hair follicles after Asc 2‐P treatment in the absence or presence of LY294002 was examined by Ki‐67 immunostaining. Results IGF‐1 mRNA in DP cells was upregulated and IGF‐1 protein in the conditioned medium of DP cells was significantly increased after treatment with Asc 2‐P. Immunohistochemical staining showed that IGF‐1 staining is increased in the DP of cultured human hair follicles by Asc 2‐P. The neutralizing antibody against IGF‐1 significantly suppressed the Asc 2‐P‐mediated elongation of hair shafts in hair follicle organ culture and significantly attenuated Asc 2‐P‐induced growth of cocultured keratinocytes. LY294002 significantly attenuated Asc 2‐P‐inducible IGF‐1 expression and proliferation of follicular keratinocytes in cultured hair follicles. Conclusions These data show that Asc 2‐P‐inducible IGF‐1 from DP cells promotes proliferation of follicular keratinocytes and stimulates hair follicle growth in vitro via PI3K.