抑制与压力相关的内质网膜 IRE-1 途径缓解了早产
Liyin Qiu1, Hui Liu2, Shali Chen1
1Department of Obstetrics, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.
在早产 (PTB) 胎盘组织中,需要伊诺西类型1 (IRE-1) 酶的升调有助于PTB的发病. 抑制与内质网膜应激 (ERS) 相关的IRE-1/XBP1/CHOP通路可能会减轻PTB.
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
- 孕产妇与胎儿的医学
背景情况:
- 早产 (PTB) 是一个与新生儿并发症相关的全球重大健康问题.
- 在细胞调节中发挥关键作用的是因诺需要酶1型 (IRE-1) 介导的未折叠蛋白质反应 (UPR).
- 了解与内质网膜应激 (ERS) 相关的IRE-1通路在PTB中的作用至关重要.
研究的目的:
- 研究与ERS相关的IRE-1通路在PTB病变发生过程中的作用.
- 评估IRE-1在ER压力条件下对胎盘 trofhoblast 细胞功能的影响.
主要方法:
- 人类胎盘 trofhoblast 细胞 (HTR8 / Svneo) 接受了突尼卡米辛 (TM) 诱导ER压力.
- 在胎盘组织和细胞中分析了IRE-1和相关蛋白质 (ATF6,GRP78,XBP-1) 的表达.
- 评估了细胞活力,迁移,入侵,细胞亡和自,使用ESR抑制剂TUDCA和IRE-1敲击的干预措施.
主要成果:
- 在PTB组织和接受TM治疗的细胞中发现了ATF6,GRP78和XBP-1的升高水平.
- TM治疗降低了细胞活力,迁移和入侵,同时增加了细胞亡; TUDCA抵消了这些影响.
- 在PTB中观察到IRE-1过度表达;IRE-1倒置改善了细胞活力,迁移和入侵,并在TM刺激下抑制了细胞亡和自,调节了IRE-1/XBP1/CHOP通路.
结论:
- 在PTB胎盘组织中升级的IRE-1与PTB发展有关.
- 针对 IRE-1/XBP1/CHOP 途径提供了缓解 PTB 的潜在治疗策略.
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