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P45
INVOLVEMENT OF SURVIVIN IN HAIR GROWTH CONTROL
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.
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