Signal transduction in human hair follicles

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One of the typical example of the signal transduction in the cell is androgen-androgen receptor system. In order to know the mode of androgen action in human hair follicles, we developed an in vitro coculture system using DPC and follicular epithelial cells. Androgen significantly stimulated the proliferation of follicular epithelial cells cocultured with beard or axillary DPC, suggesting that these DPC produce androgen-dependent diffusible growth factors. On the contrary, we could identify inhibitory roles of androgen on the growth follicular epithelial cells cocultured with DPC derived from the human bald frontal scalps, when DPC were transfected with the AR expression vector. Androgen-inducible TGF-β1 derived from DPCs plays a central role for the growth suppression.We previously established keratinocyte-specific Stat3-disrupted mice, and found that Stat3 is required for anagen progression in the hair cycle. Anagen was successfully induced even in Stat3-disrupted mice by topical application of PMA. PMA stimulated the migration of Stat3-disrupted keratinocytes in vitro. Both Stat3-dependent and independent migration of keratinocytes was inhibited by wortmannin. Therefore, anagen is mediated by at least two distinct signaling pathways : Stat3-dependent pathway for spontaneous hair cycling and Stat3-independent (probably PKC-dependent) pathway for exogenously induced hair cycling, whereas both pathways require PI3K activation.