过度表达MicroRNA-322可减少糖尿病怀孕中神经管缺陷的发生
Guanglei Wang1, Shicong Song1, Wei-Bin Shen1
1Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD.
American journal of obstetrics and gynecology
|August 2, 2023
概括
孕产妇糖尿病可以通过降低microRNA-322 (miR-322) 水平引起神经管缺陷. 恢复miR-322的表达通过抑制亡来预防这些缺陷,确定miR-322作为潜在的治疗标.
科学领域:
- 发育生物学是发展生物学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 孕期糖尿病 (GDM) 是先天性异常,特别是神经管缺陷 (NTD) 的重要危险因素.
- 虽然叶酸补充是标准的,但一些NTDs是叶酸耐药的,需要替代的预防策略.
- 微RNAs (miRNAs) 正在成为胚胎发育的关键调节者和潜在的治疗点.
研究的目的:
- 研究微RNA-322 (miR-322) 和需要伊诺西的跨膜激酶/内核酶1α (IRE1α) 在孕产妇糖尿病诱导的NTD中所起的作用.
- 确定潜在的治疗目标,以预防因糖尿病而复杂的怀孕中的NTD.
主要方法:
- 过度表达miR-322的小鼠与糖尿病和非糖尿病雌性交配,以评估NTD发病率和miR-322转录水平.
- 在实验室中对暴露在高葡萄糖条件下的小鼠神经干细胞进行研究.
- 通过使用RNA免疫沉和转染来研究IRE1α淘汰或过度表达对miR-322水平的影响.
主要成果:
- 母亲糖尿病在发育中的神经皮质中显著抑制了miR-322的表达.
- 恢复miR-322表达改善了糖尿病诱导的亡,并减少了NTD的形成.
- 激活的IRE1α被确定为一种直接降解前体miR-322的内核酶,导致成熟的miR-322水平降低和TRAF3上调.
结论:
- IRE1α-miR-322-TRAF3通路在调解神经皮质细胞亡和糖尿病怀孕中NTD发展方面发挥着关键作用.
- miR-322和IRE1α代表了预防与孕产妇糖尿病相关的NTD的有希望的治疗点.
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