通过调节PKM2的作用,HIF-1α与子宫内膜受体性积极相关
Lixia Liang1,2, Yang Yang1, Lin Yang1
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
The journal of obstetrics and gynaecology research
|August 3, 2023
概括
缺氧诱导因子-1α (HIF-1α) 对于子宫内膜受体 (ER) 和成功怀孕至关重要. 这项研究揭示了HIF-1α通过糖解调节ER基因表达,为植入失败提供了洞察力.
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
背景情况:
- 辅助生殖技术 (ART) 已经取得了显著的进步,但植入失败仍然是怀孕的主要障碍.
- 子宫内膜受容性 (ER) 对于成功的胚胎植入至关重要,但其潜在的生物机制尚未完全理解.
研究的目的:
- 调查缺氧诱导因子-1α (HIF-1α) 在建立子宫内膜受体性的作用.
- 阐明HIF-1α调节ER基因表达网络的分子机制.
主要方法:
- 在使用RT-PCR,免疫栓塞和免疫组织化学的子宫内膜组织中量化HIF-1α,HOXA10,IGFBP1,PKM2和LDHA的水平.
- 分析了HIF-1α和关键的子宫内膜受容性标志物之间的相关性.
- 利用石川细胞模型与HIF-1α和PKM2操纵来评估基因表达,乳酸生产和细胞迁移.
主要成果:
- 在复发性植入失败 (RIF) 患者中,HIF-1α,HOXA10,IGFBP1,PKM2和LDHA水平显著降低.
- HOXA10,IGFBP1,PKM2和LDHA的表达与子宫内膜中的HIF-1α水平相关.
- 在细胞模型中的HIF-1α操纵改变了HOXA10,IGFBP1,LDHA,PKM2表达和乳酸度,而PKM2-siRNA减少了HOXA10和IGFBP1表达.
结论:
- 缺氧诱导因子-1α (HIF-1α) 在子宫内膜受体 (ER) 发育中起着至关重要的作用.
- HIF-1α通过调节糖解来调节ER,影响关键的基因表达网络.
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