细胞内膜网膜应激会在分娩开始期间通过调节CYLD诱导热囊细胞烧灭
Xiaolei Zhang1, Meitao Yang2, Dan Lv3
1Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gynecology and Obstetrics, Guizhou Provincial People's Hospital, Guizhou, China.
细胞内膜网膜应激 (ERS) 和圆柱体瘤 (CYLD) 驱动了热囊细胞热,这是早产 (PTB) 的关键机制. 调节ERS和CYLD为预防PTB提供了一个潜在的治疗目标.
科学领域:
- 生殖生物学 生殖生物学
- 细胞应激反应细胞应激反应
- 炎症信号传递是炎症信号.
背景情况:
- 过早分娩 (PTB) 对新生儿的健康构成重大风险.
- 母胎炎症和内细胞网膜应激 (ERS) 与PTB发病有关.
- 导致PTB的精确分子机制尚不清楚.
研究的目的:
- 为了调查来自终期和早产怀孕的胎盘组织中的ERS水平.
- 为了检查ERS和圆柱状瘤病 (CYLD) 在 trofhoblast pyroptosis 中的作用.
- 阐明导致PTB的分子机制.
主要方法:
- 招募了60名孕妇参加期末分娩 (TL),期末非分娩 (TNL),早产 (PTL) 和早产非分娩 (PTNL) 组.
- 评估了ESR的蛋白质和mRNA水平,烟灭菌标记物和CYLD,使用西式涂抹,免疫组织化学,免疫光和实时PCR.
- 建立了体外炎症热囊细胞模型,并使用Thapsigargin (TG) 和Tauroursodeoxycholate (TUDCA) 调节了ERS.
主要成果:
- 在与PTB相关的组和炎症模型中发现了升高的ERS和热的标志物.
- 塔普西加丁 (TG) 增加了CYLD表达和诱导了热囊细胞热; 塔乌鲁索德氧化酸盐 (TUDCA) 减轻了这些影响.
- 沉默CYLD降低了热致死,而其过度表达则抵消了TUDCA的抑制作用.
结论:
- 通过CYLD介导的ERS介导的 trofhoblast pyroptosis 在炎症条件下与PTB有关.
- 这一途径为调节分娩开始提供了潜在的治疗点.
- 了解这些机制对于解决PTB并发症至关重要.
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