在决定化过程中,miRNA与内细胞网膜应激和展开的蛋白质反应相关
Elizabeth Soczewski1, José Martin Murrieta-Coxca2, Lucas Miranda1
1CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales IQUIBICEN, Buenos Aires, Argentina.
Reproductive biomedicine online
|September 1, 2023
概括
像miR-17-5p,miR-21-5p和miR-193b-3p这样的microRNAs (miRNAs) 可能会调节细胞内膜网膜应激 (ERS) 和决定化的细胞中的炎症. 它们在患有生殖功能衰竭的患者中的改变表达表明它们在植入问题中的作用.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 细胞应激反应的细胞应激反应
背景情况:
- 细胞内膜网膜应激 (ERS) 和未折叠的蛋白质反应 (UPR) 在决定化的细胞中至关重要.
- 这些途径的失调与生殖失败有关,例如复发性怀孕失败 (RPL) 和复发性植入失败 (RIF).
研究的目的:
- 研究微RNAs (miRNAs) 在决定性细胞中调节ERS和UPR中的作用.
- 探索miRNA表达和生殖失败之间的关联.
主要方法:
- 用8-Br-cAMP进行子宫内膜层细胞 (St-T1b) 的体外结核化.
- 使用thapsigargin.gin进行ERS诱导.
- 对于ERS传感器,UPR标记物和miRNA表达的定量PCR.
- 在分析以确定潜在的miRNA调节器.
- 在RPL和RIF患者的子宫内膜活检上的in-situ杂交.
主要成果:
- 决定化增加了ERS传感器 (ATF6α,PERK,IRE1α) 和UPR标志物 (CHOP) 的表达.
- 在决定化过程中,炎症标志物 (TXNIP,NLRP3,IL-1β) 的上调.
- 确定了miR-17-5p,miR-21-5p和miR-193b-3p作为ERS/UPR和炎症的潜在调节剂.
- 这些miRNAs显示在thapsigargin治疗的非决定化细胞中的表达减少.
- 这些miRNAs的差异表达被观察到来自RPL和RIF患者的 stromal细胞中,在RPL表达较低.
结论:
- 决定化涉及ESR/UPR和潜在由特定miRNAs调节的炎症过程.
- 患有生殖功能衰竭的患者体内细胞中miR-17-5p,miR-21-5p和miR-193b-3p的改变表达表明在调节ERS/UPR通路方面发挥了作用.
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