CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD2

Cells. 2023 Feb 9;12(4):555. doi: 10.3390/cells12040555.

Abstract

The number of people suffering from hair loss is increasing, and hair loss occurs not only in older men but also in women and young people. Prostaglandin D2 (PGD2) is a well-known alopecia inducer. However, the mechanism by which PGD2 induces alopecia is poorly understood. In this study, we characterized CXXC5, a negative regulator of the Wnt/β-catenin pathway, as a mediator for hair loss by PGD2. The hair loss by PGD2 was restored by Cxxc5 knock-out or treatment of protein transduction domain-Dishevelled binding motif (PTD-DBM), a peptide activating the Wnt/β-catenin pathway via interference with the Dishevelled (Dvl) binding function of CXXC5. In addition, suppression of neogenic hair growth by PGD2 was also overcome by PTD-DBM treatment or Cxxc5 knock-out as shown by the wound-induced hair neogenesis (WIHN) model. Moreover, we found that CXXC5 also mediates DHT-induced hair loss via PGD2. DHT-induced hair loss was alleviated by inhibition of both GSK-3β and CXXC5 functions. Overall, CXXC5 mediates the hair loss by the DHT-PGD2 axis through suppression of Wnt/β-catenin signaling.

Keywords: CXXC5; DHT; PGD2; Wnt/β-catenin pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Alopecia
  • DNA-Binding Proteins
  • Female
  • Glycogen Synthase Kinase 3 beta
  • Hair / metabolism
  • Humans
  • Male
  • Preimplantation Diagnosis*
  • Transcription Factors
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • CXXC5 protein, human
  • DNA-Binding Proteins
  • Glycogen Synthase Kinase 3 beta
  • Transcription Factors

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (2019R1A2C3002751, 2020M3E5E2040018). Y.C.R. was supported by a Brain Korea 21 (BK21) Plus studentship from the NRF.