Photobiomodulation therapy for hair regeneration: A synergetic activation of β-CATENIN in hair follicle stem cells by ROS and paracrine WNTs

Photobiomodulation therapy (PBMT) has shown encouraging results in the treatment of hair loss. However, the mechanism by which PBMT controls cell behavior to coordinate hair cycle is unclear. Here, PBMT is found to drive quiescent hair follicle stem cell (HFSC) activation and alleviate hair follicle atrophy. Mechanistically, PBMT triggers a new hair cycle by upregulating ll-CATENIN expression in HFSCs. Loss of bCatenin (Ctnnb1) in HFSCs blocked PBMT-induced hair regeneration. Additionally, we show PBMT-induced reactive oxygen species (ROS) activate the PI3K/AKT/GSK-3llsignaling pathway to inhibit proteasome degradation of ll-CATENIN in HFSCs. Furthermore, PBMT promotes the expression and secretion of WNTs in skin-derived precursors (SKPs) to further activate the ll-CATENIN signal in HFSCs. By contrast, eliminating ROS or inhibiting WNT secretion attenuates the activation of HFSCs triggered by PBMT. Collectively, our work suggests that PBMT promotes hair regeneration through synergetic activation of ll-CATENIN in HFSCs by ROS and paracrine WNTs by SKPs.