向VDAC1依赖的mtDNA释放减弱了纤维细胞先天性免疫激活和白风病原体的产生
Jinpeng Lv1, Huansha Zhang1, Wenhao Yu1
1Jiangsu Provincial Engineering Research Center for Drug Intelligent Manufacturing and Precision Delivery, School of Pharmacy, Changzhou University, Changzhou 213000, China.
International immunopharmacology
|February 21, 2026
概括
在白风中,氧化应激通过线粒体DNA释放激活皮肤纤维细胞,驱动炎症. 抑制VDAC1寡合化为白风治疗提供了一个潜在的治疗策略.
科学领域:
- 皮肤病学 皮肤病学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- Vitiligo 是一种慢性皮肤脱色障碍,与氧化应激和免疫失调有关.
- 虽然研究了黑色素细胞缺陷,但皮肤纤维细胞在白风病原发生过程中的作用尚不清楚.
- 皮肤纤维细胞是皮肤免疫力和对氧化应激反应的关键调节者.
研究的目的:
- 调查皮肤纤维细胞在氧化应激下白风病原发生中的作用.
- 确定将氧化应激与纤维细胞中免疫激活联系在一起的机制.
- 探索VDAC1依赖的线粒体DNA释放作为白风的治疗点.
主要方法:
- 正常的人体皮肤纤维细胞 (NHDFs) 受到亚毒性氧化应激 (过氧化).
- 分析了VDAC1的寡合化,线粒体DNA (mtDNA) 的释放,以及下游的炎症途径 (cGAS-STING,NLRP3炎症体).
- 使用药理剂来调节VDAC1和mtDNA释放.
- 在白风小鼠模型中测试了治疗疗效.
主要成果:
- 亚毒性氧化应激诱导了从结构完整的纤维细胞中VDAC1依赖的mtDNA的非亡性释放.
- 释放的mtDNA激活了cGAS-STING和NLRP3炎症体通路,促进了炎症表型 (IL-1β,IL-6,ICAM-1).
- 在白风小鼠模型中,用VBIT-4抑制VDAC1寡合化可以防止mtDNA泄漏,减少纤维细胞衰老和炎症,改善皮肤再发色.
结论:
- 皮肤纤维细胞通过VDAC1-mtDNA-cGAS-STING通路作为氧化应激的传感器和放大器.
- VDAC1依赖的mtDNA释放是白风中纤维细胞介导的先天免疫激活的一个上游事件.
- 针对VDAC1寡合化,为白风提供了一种新的治疗策略.
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