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

Stem Cell Reports. 2021 Jun 8;16(6):1568-1583. doi: 10.1016/j.stemcr.2021.04.015. Epub 2021 May 20.

Abstract

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 β-CATENIN expression in HFSCs. Loss of β-Catenin (Ctnnb1) in HFSCs blocked PBMT-induced hair regeneration. Additionally, we show PBMT-induced reactive oxygen species (ROS) activate the PI3K/AKT/GSK-3β signaling pathway to inhibit proteasome degradation of β-CATENIN in HFSCs. Furthermore, PBMT promotes the expression and secretion of WNTs in skin-derived precursors (SKPs) to further activate the β-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 β-CATENIN in HFSCs by ROS and paracrine WNTs by SKPs.

Keywords: GSK-3β/β-CATENIN; hair follicle stem cells; hair regeneration; photobiomodulation therapy; skin-derived precursors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / therapy*
  • Animals
  • Female
  • Gene Expression Regulation
  • Gene Knockout Techniques / methods
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hair Follicle / metabolism*
  • Low-Level Light Therapy / methods*
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / metabolism
  • Reactive Oxygen Species / metabolism*
  • Regeneration
  • Stem Cells / metabolism*
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism*

Substances

  • Reactive Oxygen Species
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta