Dataset Information

CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD₂.

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.

SUBMITTER: Ryu YC

PROVIDER: S-EPMC9954685 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD2.

Ryu Yeong Chan YC Park Jiyeon J Kim You-Rin YR Choi Sehee S Kim Geon-Uk GU Kim Eunhwan E Hwang Yumi Y Kim Heejene H Han Gyoonhee G Lee Soung-Hoon SH Choi Kang-Yell KY

Cells 20230209 4

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 Cxx ...[more]

PMID: 36831222

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Project description:BackgroundAndrogenetic alopecia (AGA) is the most common form of hair loss. Studies have suggested a potential link to metabolic disorders, but with conflicting results. To elucidate the lipidomics profile and sex-specific variations in AGA, while exploring correlation between AGA and metabolic syndrome (MetS).MethodsThe AGA patients (n = 83) and healthy controls (n = 84) were collected in the study. The lipid profiles were analyzed using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Serum levels of important factors associated with AGA, namely dihydrotestosterone (DHT), prostaglandin D2 (PGD2) and transforming growth factor-β1 (TGF-β1) were quantified using ELISA.ResultsCompared with controls, AGA patients had a higher probability of MetS (26.51% vs 11.9%, P < 0.05). Fifty-one differentially expressed lipids were identified in AGA. The kind of triglyceride (TG) were significantly increased, while phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) exhibited remarkable decrease. PC (16:2/21:6), PC (34:4p), PE (41:7), PE (44:12), PG (40:9), PI (32:2) and TG (15:0/18:1/18:1) were identified as potential biomarkers of AGA with the highest specificity. The levels of DHT, PGD2 and TGF-β1 were significantly elevated in AGA. All seven lipids showed significant correlations with DHT, PC (34:4p) and TG (15:0/18:1/18:1) were significantly associated with PGD2, TGF-β1 displayed exclusively correlation with TG (15:0/18:1/18:1) (all P < 0.05). Furthermore, these lipids were also significantly linked to systolic blood pressure and BMI, while some of them also showed significant associations with total cholesterol and HDL-C. In subgroups, forty-two differentially expressed lipids were identified in male AGA vs male control and eighty-one in female AGA vs female control. PC (16:2/21:6) was the only specific lipids common to both sexes.ConclusionsAberrant lipid metabolism was observed in AGA, with distinct lipidomic profiles between male and female AGA. The potential biomarkers were closely related to DHT, PGD2, TGF-β1 and MetS-related indicators. It provides the foundation for revealing the mechanisms of AGA.

Dataset Information

CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD₂.

Publications

CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD<sub>2</sub>.

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