3.      Induction of versican by ascorbic acid 2-phosphate in dermal papilla cells.
Moon-Kyu Kim, Soon-Re Kim, Jung-Chul Kim, Young-Kwan Sung,  Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea

We have recently reported that L-ascorbic acid 2-phosphate magnesium salt (Asc 2-P), a derivative of L-ascorbic acid (Vitamin C), promotes the elongation of hair shafts in hair follicles in culture and induces early conversion from a telogen phase to an anagen phase in mice, demonstrating that Asc 2-P affects hair growth and cycling. Here, we investigated whether Asc 2-P regulates expression of versican, which is thought to play an important role in anagen induction and maintenance of the normal hair growth, in cultured dermal papilla cells and in dermal papilla of isolated hair follicles in culture. Hair biopsy specimens were obtained from the non-balding occipital scalp region of patients with androgenic alopecia. Dermal papilla cells of the 2~3 passage were used in this study. Immunohistochemical staining of versican was performed with rabbit polyclonal antibody recognizing versican V0 and V1 isoforms. We observed that isoforms of versican were up-regulated in dermal papilla cells by Asc 2-P treatment. Immunohistochemical staining also revealed increased expression of versican, at least V0 and V1, in dermal papilla of isolated hair follicles treated with Asc 2-P. LY294002, a pharmacological inhibitor of PI3K, significantly attenuated Asc 2-P-induced versican expression. We also observed that Asc 2-P activates/phosphorylates PKB, a downstream effector of PI3K, and that LY294002 attenuates Asc 2-P-mediated phosphorylation of PKB. In addition, we observed that nuclear beta-catenin is increased by Asc 2-P in a dose-dependent manner and LY294002 reduces nuclear accumulation of beta-catenin. This study demonstrates that Asc 2-P induces versican expression via PI3K signaling and causes nuclear beta-catenin accumulation in dermal papilla cells. Since versican is thought to play an important role in anagen induction and maintenance of the normal hair growth, it would be worthy to evaluate vitamin C or its derivatives as a novel approach for treatment and prevention of hair loss.