CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub>
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 D<sub>2</sub> (PGD<sub>2</sub>) is a well-known alopecia inducer. However, the mechanism by which PGD<sub>2</sub&...
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2023-02-01
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| author | Yeong Chan Ryu Jiyeon Park You-Rin Kim Sehee Choi Geon-Uk Kim Eunhwan Kim Yumi Hwang Heejene Kim Gyoonhee Han Soung-Hoon Lee Kang-Yell Choi |
| author_facet | Yeong Chan Ryu Jiyeon Park You-Rin Kim Sehee Choi Geon-Uk Kim Eunhwan Kim Yumi Hwang Heejene Kim Gyoonhee Han Soung-Hoon Lee Kang-Yell Choi |
| author_sort | Yeong Chan Ryu |
| collection | DOAJ |
| container_title | Cells |
| description | 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 D<sub>2</sub> (PGD<sub>2</sub>) is a well-known alopecia inducer. However, the mechanism by which PGD<sub>2</sub> 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 PGD<sub>2</sub>. The hair loss by PGD<sub>2</sub> was restored by <i>Cxxc5</i> 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 PGD<sub>2</sub> was also overcome by PTD-DBM treatment or <i>Cxxc5</i> knock-out as shown by the wound-induced hair neogenesis (WIHN) model. Moreover, we found that CXXC5 also mediates DHT-induced hair loss via PGD<sub>2</sub>. DHT-induced hair loss was alleviated by inhibition of both GSK-3β and CXXC5 functions. Overall, CXXC5 mediates the hair loss by the DHT-PGD<sub>2</sub> axis through suppression of Wnt/β-catenin signaling. |
| format | Article |
| id | doaj-art-e748a3a88dce4e9dbe31c94e1e347d31 |
| institution | Directory of Open Access Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-e748a3a88dce4e9dbe31c94e1e347d312025-08-19T22:43:23ZengMDPI AGCells2073-44092023-02-0112455510.3390/cells12040555CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub>Yeong Chan Ryu0Jiyeon Park1You-Rin Kim2Sehee Choi3Geon-Uk Kim4Eunhwan Kim5Yumi Hwang6Heejene Kim7Gyoonhee Han8Soung-Hoon Lee9Kang-Yell Choi10Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaCK Regeon Inc., B137 Engineering Research Park, 50 Yonsei Ro, Seoul 03722, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaThe 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 D<sub>2</sub> (PGD<sub>2</sub>) is a well-known alopecia inducer. However, the mechanism by which PGD<sub>2</sub> 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 PGD<sub>2</sub>. The hair loss by PGD<sub>2</sub> was restored by <i>Cxxc5</i> 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 PGD<sub>2</sub> was also overcome by PTD-DBM treatment or <i>Cxxc5</i> knock-out as shown by the wound-induced hair neogenesis (WIHN) model. Moreover, we found that CXXC5 also mediates DHT-induced hair loss via PGD<sub>2</sub>. DHT-induced hair loss was alleviated by inhibition of both GSK-3β and CXXC5 functions. Overall, CXXC5 mediates the hair loss by the DHT-PGD<sub>2</sub> axis through suppression of Wnt/β-catenin signaling.https://www.mdpi.com/2073-4409/12/4/555PGD<sub>2</sub>CXXC5Wnt/β-catenin pathwayDHT |
| spellingShingle | Yeong Chan Ryu Jiyeon Park You-Rin Kim Sehee Choi Geon-Uk Kim Eunhwan Kim Yumi Hwang Heejene Kim Gyoonhee Han Soung-Hoon Lee Kang-Yell Choi CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub> PGD<sub>2</sub> CXXC5 Wnt/β-catenin pathway DHT |
| title | CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub> |
| title_full | CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub> |
| title_fullStr | CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub> |
| title_full_unstemmed | CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub> |
| title_short | CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub> |
| title_sort | cxxc5 mediates dht induced androgenetic alopecia via pgd sub 2 sub |
| topic | PGD<sub>2</sub> CXXC5 Wnt/β-catenin pathway DHT |
| url | https://www.mdpi.com/2073-4409/12/4/555 |
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