Xiong Renxue, Jin Shiyu, Li Yujie, Dong Tingru, Song Xiuzu, Guan Cuiping
Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou, China.
Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Biochim Biophys Acta Mol Cell Res. 2025 Oct;1872(7):119995. doi: 10.1016/j.bbamcr.2025.119995. Epub 2025 May 30.
Oxidative stress plays a significant role in the development of vitiligo. Although the specific mechanism of the mitochondria-targeted antioxidant mitoquinone (MitoQ) in vitiligo remains unclear, it has shown promise in the treatment of various diseases.
In this study, we employed network pharmacology, molecular docking, transcriptomic approaches, and experimental verification to investigate the potential targets of MitoQ in vitiligo.
Molecular docking results identified four possible crucial targets of MitoQ in vitiligo treatment: poly (ADP-ribose) polymerase 1 (PARP1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), and C-X-C motif chemokine receptor 3 (CXCR3). MitoQ alleviated oxidative stress-induced PARP1 nuclear mislocalization, attenuated ROS accumulation, restored mitochondrial membrane potential, and enhanced ATP synthesis in vitro analysis. Transcriptomic analysis demonstrated that MitoQ reduced the expression of DNA damage genes and genes involved in the PI3K-AKT and MAPK signaling pathways. The protein-protein interaction network indicated a potential relationship between PARP1 and DNA damage-related genes, suggesting that MitoQ could interfere with abnormal PARP1 activation. Notably, MitoQ reduced cellular senescence by decreasing CDKN1A/p21 protein through PARP1, and the knockdown of PARP1 reduced oxidative damage.
These results indicate that PARP1 decreases cellular senescence and offers a potential target for therapeutic research in the management of vitiligo.
氧化应激在白癜风的发展中起重要作用。尽管线粒体靶向抗氧化剂米托醌（MitoQ）在白癜风中的具体机制尚不清楚，但它在治疗各种疾病方面已显示出前景。
在本研究中，我们采用网络药理学、分子对接、转录组学方法和实验验证来研究MitoQ在白癜风中的潜在靶点。
分子对接结果确定了MitoQ在白癜风治疗中的四个可能的关键靶点：聚（ADP - 核糖）聚合酶1（PARP1）、前列腺素内过氧化物合酶2（PTGS2）、雌激素受体1（ESR1）和C - X - C基序趋化因子受体3（CXCR3）。体外分析显示，MitoQ减轻了氧化应激诱导的PARP1核错位，减少了活性氧积累，恢复了线粒体膜电位，并增强了ATP合成。转录组分析表明，MitoQ降低了DNA损伤基因以及参与PI3K - AKT和MAPK信号通路的基因的表达。蛋白质 - 蛋白质相互作用网络表明PARP1与DNA损伤相关基因之间存在潜在关系，提示MitoQ可能干扰PARP1的异常激活。值得注意的是，MitoQ通过PARP1降低CDKN1A/p21蛋白从而减少细胞衰老，而PARP1的敲低减少了氧化损伤。
这些结果表明PARP1可减少细胞衰老，并为白癜风治疗研究提供了一个潜在靶点。
