Botchkareva NV, Ahluwalia G, Shander D
Gillette Technology Center, Needham, MA, USA

Hair follicle growth is maintained by rapid proliferation of the hair matrix keratinocytes, while the cessation of proliferative activity alone or in concert with activation of apoptosis leads to hair growth retardation and/or to hair follicle involution (catagen). However, molecular mechanisms that control proliferation of the hair matrix keratinocytes remain largely unknown. Survivin is a bi-functional protein that belongs to the inhibitor of apoptosis (IAP) protein family. Survivin is essential for the proper control of cell proliferation, as well as for suppression of apoptosis in proliferating cells. Here, we explored the role of survivin in the control of cell proliferation during the hair follicle growth. By multi-color immunofluorescence, survivin expression was seen in proliferating Ki-67 positive cells of the hair matrix and outer root sheath of human scalp and beard anagen hair follicles, as well as in distinct epidermal keratinocytes. Interestingly that hair matrix keratinocytes showed the higher levels of survivin expression, compared to the epidermal cells. In hair follicle organ culture, the reduction of survivin protein levels resulted in a substantial reduction of hair growth rate. By ELISA, the significant (p<0.01) decrease of the survivin protein levels was seen in the hair follicles treated with Cdk inhibitor, roscovitin, compared to the controls. The reduction of survivin levels in the hair follicles after roscovitin treatment resulted in a significant (p<0.05) decrease in the hair growth rate. In addition, down-regulation of the survivin levels after treatment with beta-catenin inhibitor also resulted in significant reduction of the hair growth rate (p<0.01). Thus, these data suggest the important role for survivin in the control of cell proliferation in human anagen hair follicles, and raise a possibility for using the inhibitors of survivin activity for pharmacological modulation of the hair growth.