Two Distinct Signaling Pathways in Hair Cycle Induction: Stat3-Dependent and Independent Pathways

The study investigated the role of signal transducer and activator of transcription 3 (Stat3) in hair cycle progression by using keratinocyte-specific Stat3-disrupted mice. The researchers found that although Stat3 is necessary for wound healing and spontaneous anagen progression in the hair cycle, it is not required for experimentally induced anagen. Both chemical (phorbol 12-myristate 13-acetate, PMA) and mechanical (hair plucking) stimulations successfully induced anagen in Stat3-disrupted and wild-type mice, suggesting the existence of a Stat3-independent pathway for hair cycle induction. This alternative pathway is likely to be protein kinase C (PKC)-dependent, as PMA stimulated the migration of Stat3-disrupted keratinocytes in vitro. However, both Stat3-dependent and independent pathways were found to require phosphoinositide 3-kinase (PI3K) activation, as their migration was inhibited by the PI3K inhibitor wortmannin. The study concludes that there are at least two distinct signaling pathways for anagen entry: a Stat3-dependent pathway for natural hair cycling and a Stat3-independent pathway for hair cycle induction by external stimuli, with both pathways necessitating PI3K activation.