CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD2

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 characte...

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Published in:Cells (Basel, Switzerland) Switzerland), 2023-02, Vol.12 (4), p.555
Main Authors: Ryu, Yeong Chan, Park, Jiyeon, Kim, You-Rin, Choi, Sehee, Kim, Geon-Uk, Kim, Eunhwan, Hwang, Yumi, Kim, Heejene, Han, Gyoonhee, Lee, Soung-Hoon, Choi, Kang-Yell
Format: Article
Language:English
Subjects:
Alopecia
Antibodies
Baldness
CXXC5
Cytokeratin
DHT
Dishevelled protein
Hair
Hair loss
PGD2
Prostaglandin D2
Proteins
Signal transduction
Wnt protein
Wnt/β-catenin pathway
β-Catenin
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells12040555