Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
CK Regeon Inc., B137 Engineering Research Park, 50 Yonsei Ro, Seoul 03722, Republic of Korea.
Cells. 2023 Feb 9;12(4):555. doi: 10.3390/cells12040555.
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 (PGD) is a well-known alopecia inducer. However, the mechanism by which PGD 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. The hair loss by PGD was restored by 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 was also overcome by PTD-DBM treatment or 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. 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 axis through suppression of Wnt/β-catenin signaling.
脱发的人数正在增加，脱发不仅发生在老年男性中，也发生在女性和年轻人中。前列腺素 D (PGD) 是一种众所周知的脱发诱导剂。然而，PGD 诱导脱发的机制尚不清楚。在这项研究中，我们将 CXXC5 鉴定为 PGD 诱导脱发的负调控因子，CXXC5 是 Wnt/β-连环蛋白途径的负调节剂。PGD 引起的脱发可通过敲除或蛋白转导结构域-Dishevelled 结合基序 (PTD-DBM) 治疗得到恢复，PTD-DBM 是一种通过干扰 CXXC5 与 Dishevelled (Dvl) 的结合功能来激活 Wnt/β-连环蛋白途径的肽。此外，如伤口诱导的毛发生长（WIHN）模型所示，PGD 抑制新生毛发生长也可通过 PTD-DBM 治疗或敲除来克服。此外，我们发现 CXXC5 还通过 PGD 介导 DHT 诱导的脱发。抑制 GSK-3β 和 CXXC5 的功能均可减轻 DHT 诱导的脱发。总的来说，CXXC5 通过抑制 Wnt/β-连环蛋白信号通路介导 DHT-PGD 轴诱导的脱发。
