Irisin promotes hair growth and hair cycle transition by activating the GSK-3β/β-catenin pathway

Exp Dermatol. 2024 Aug;33(8):e15155. doi: 10.1111/exd.15155.

Abstract

Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF-1, FGF and irisin are reprehensive myokines. Although VEGF, IGF-1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/β-catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF-1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/β-catenin signalling inhibitor, suppressed the irisin-mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/β-catenin pathway and highlight its therapeutic potential in hair loss treatment.

Keywords: Irisin; Wnt/β‐catenin; hair loss; human dermal papilla cells; myokine.

MeSH terms

  • Animals
  • Cell Proliferation
  • Female
  • Fibronectins* / metabolism
  • Glycogen Synthase Kinase 3 beta* / metabolism
  • Hair Follicle* / growth & development
  • Hair Follicle* / metabolism
  • Hair* / growth & development
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Proto-Oncogene Proteins
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*
  • Wnt-5a Protein / metabolism
  • beta Catenin* / metabolism

Substances

  • Fibronectins
  • FNDC5 protein, human
  • Glycogen Synthase Kinase 3 beta
  • beta Catenin
  • Lymphoid Enhancer-Binding Factor 1
  • WNT10B protein, human
  • Wnt-5a Protein
  • LEF1 protein, human
  • Wnt Proteins
  • FNDC5 protein, mouse
  • Wnt10b protein, mouse
  • GSK3B protein, human
  • CTNNB1 protein, human
  • Proto-Oncogene Proteins