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皮的自身抗体诱导ER应激反应
bioRxiv : the preprint server for biology
|September 4, 2024
概括
黄虫 (Pemphigus vulgaris,PV) 的自身抗体会触发细胞内网膜 (ER) 的压力,破坏脱体和细胞粘附. 抑制ER压力对治疗这种水泡性皮肤疾病充满希望.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
背景情况:
- 德斯莫索姆对皮肤完整性至关重要.
- 黄 (Pemphigus vulgaris) (PV) 涉及到针对desmoglein 3 (Dsg3) 的自身抗体,导致水泡形成.
- 背后的分子机制是不清楚的PV诱导的desmosome损失.
研究的目的:
- 为了研究内细胞网膜 (ER) 应激在PV病原发生中的作用.
- 为了确定参与PV诱导的细胞粘附损失的分子信号通路.
主要方法:
- 用PV患者IgG治疗的角质细胞的高分辨率时间延迟成像.
- 生物化学测试来评估ER压力信号通路 (IRE1,PERK).
- 在PV患者皮肤样本中分析ER压力转录.
- 药理上抑制ER压力以评估其治疗潜力.
主要成果:
- 在ER管道和内部化Dsg3之间,PV IgG诱导了持续接触.
- 在 keratinocytes 中,PV IgG 激活了 ER 应激通路 (IRE1,PERK).
- 在PV患者皮肤中,ER压力成绩单升高.
- 抑制ER应激保护免受PV IgG诱导的脱体破坏和角质细胞脱落.
结论:
- ER压力是Pemphigus vulgaris的一个关键病理机制.
- 德斯莫索姆粘附可以与ER功能集成,作为应力传感器.
- 针对ER压力路径为PV提供了潜在的治疗策略.
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