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SHP2 调节了人类子宫内膜细胞中 HIF-1 信号通路†

Liqun Ouyang¹, Xia Gao¹, Rongyu Yang¹

¹Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University, Xiangan South Road, Xiamen, Fujian 361102, China.

Biology of reproduction

|February 2, 2025

概括

蛋白质氨酸酸酶2 (SHP2) 通过与低氧诱导因子-1 (HIF-1) 信号通路相互作用,调节人体叶层细胞功能,影响子宫受容性和怀孕.

科学领域:

生殖生物学生殖生物学
细胞信号传递细胞信号传递
分子内分泌学分子内分泌学

背景情况:

果断性子宫内膜 stromal 细胞对于人类子宫的受容性和怀孕的建立至关重要.
蛋白氨酸酸酶2 (SHP2) 在决定化的细胞中高度表达,并影响决定化.
SHP2在果叶细胞功能中的确切作用和机制在很大程度上仍未被阐明.

研究的目的:

为了研究SHP2在人类树叶细胞中的功能和机制.
在决定化的背景下,识别由SHP2介导的信号通路.
阐明SHP2与低氧诱导因子-1 (HIF-1) 信号传递之间的相互作用.

主要方法:

靠近依赖生物化 (BioID) 用于选SHP2相互作用蛋白.
同免疫沉 (Co-IP) 证实蛋白相互作用和局部化.
定量PCR和西式斑点测试用于评估基因和蛋白质表达.
建立细胞研究的缺氧模型.
染色体免疫沉 (ChIP) 用于分析促进体结合.

主要成果:

SHP2与HIF-1α相互作用,这两种蛋白质都在状细胞的细胞核中同位.
SHP2表达与HIF-1α转录活性及其下游基因 (Eno3,Pkm2,Aldoc,Glut1) 有积极的相关性.
缺少或抑制SHP2会降低HIF-1α水平,下游基因表达和乳酸生产.
缺氧条件诱导SHP2和HIF-1α的表达,SHP2拯救SHP2-缺陷效应.
SHP2直接与HIF-1α及其向基因的促进子区域结合.

结论:

通过HIF-1α信号通路,SHP2在调节人类叶 stromal 细胞功能方面发挥着重要作用.
这项研究揭示了一种新的机制,SHP2通过它影响着果细胞功能,影响子宫受体.
针对SHP2-HIF-1α轴可能为与怀孕有关的疾病提供新的治疗策略.

关键词:

在HIF-1信号通道中,在 SHP2 中, SHP2 是 SHP2.个人化的决定性.胚胎内膜的 stromal 细胞.缺氧缺氧是指缺氧的情况.

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