通过WTAPP1进行表观遗传调节,通过CNR1/NF-κB激活促进妊娠糖尿病中热囊细胞功能障碍
Na Yang1, Yuan Li2, Jiefang Zhang2
1Internal Medicine, The Fourth Hospital of Shijiazhuang, No. 206, Zhongshan East Road, Chang'an District, Shijiazhuang, 050000, Hebei, China. 13731190566@163.com.
European journal of medical research
|October 15, 2025
概括
孕期糖尿病 (GDM) 涉及到胎盘组织中增加的威尔姆斯瘤1相关蛋白质伪基1 (WTAPP1). WTAPP1通过大麻素受体1的m6A甲基化驱动 trofhoblast 细胞损伤,提供了一个潜在的治疗标.
科学领域:
- 生殖生物学 生殖生物学
- 分子内分泌学分子内分泌学
- 细胞病理学细胞病理学
背景情况:
- 孕期糖尿病 (GDM) 对母亲和胎儿的健康有重大风险.
- 了解与GDM相关的胎盘功能障碍的分子基础对于开发有效的干预措施至关重要.
研究的目的:
- 调查威尔姆斯瘤1相关蛋白伪基1 (WTAPP1) 在GDM诱导的胎盘损伤中的作用.
- 在高葡萄糖环境中,阐明将WTAPP1与热囊细胞损伤联系起来的分子机制.
主要方法:
- 从GDM患者和对照组的胎盘组织分析.
- 在体外研究中,使用暴露于高葡萄糖的HTR-8/Svneo trofhoblast细胞.
- 评估氧化应激,炎症,亡和基因表达.
- WTAPP1的淘汰和救援实验,包括CNR1过度表达和NF-κB抑制.
主要成果:
- 在GDM胎盘组织中,WTAPP1被显著上调,与禁食葡萄糖水平相关.
- 高葡萄糖诱导的氧化应激,炎症和热囊细胞的亡,效应被WTAPP1敲击部分逆转.
- WTAPP1通过WTAP介导的m6A甲基化促进了大麻素受体1 (CNR1) 表达,激活了NF-κB信号传递.
- 证实CNR1和NF-κB信号传递是高葡萄糖诱导的热囊细胞损伤的关键媒介.
结论:
- 一个新的WTAPP1/WTAP-m6A-CNR1-NF-κB信号轴有助于GDM中 trofhoblast细胞损伤.
- 在GDM中,WTAPP1代表了减轻高血糖引起的胎盘损伤的潜在治疗标.
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