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缺氧状况会影响子宫内膜层细胞的转录组在子宫内膜异位症中,并促进TGFBI轴

Meruert Sarsenova^1,2,3, Nageswara Rao Boggavarapu², Keiu Kask^1,3

¹Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.

Frontiers in endocrinology

|January 2, 2025

概括

缺氧会改变子宫内膜异位症细胞中的基因表达. 转化生长因子β诱导 (TGFBI) 在缺氧下在异位子宫内膜细胞上调,这表明它是内膜异位症的潜在治疗点.

科学领域:

生殖医学生殖医学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

子宫内膜异位症涉及异位子宫内膜细胞生长,导致疼痛和不孕.
病变通常在缺氧腹腔中生长,影响细胞过程.
缺氧会影响基因表达和蛋白激酶 (PK) 活性.

研究的目的:

为了研究低氧诱导的转录组和PK活动在eutopic和ectopic子宫内膜的变化.
在低氧环境中识别潜在的子宫内膜异位症进展的分子机制.

主要方法:

在低氧 (1% O2) 或正常氧 (20% O2) 条件下培养了欧托皮和异位子宫内膜层细胞 (EuESCs, EcESCs).
蛋白激酶活性和转录组使用激酶试验和mRNA-seq.分析.
转化生长因子β诱导 (TGFBI) 表达通过ELISA,RT-qPCR和免疫组织化学量化.

主要成果:

缺氧降低了PKAc和Akt的活性,并在EcESC中增加了Rho依赖PK (ROCK) 的活性.
低氧状态下的EuESC显示了与有氧糖解和新陈代谢相关的高调基因.
在缺氧状态下,EcESCs独特地调高了TGFBI;在缺氧状态下,TGFBI在生殖细胞中也升高,在正常状态下,生殖细胞与生殖细胞相比,生殖细胞中也升高.
在EcESC培养和低EuESC培养中观察到TGFBI分泌量的增加.
在子宫内膜组织中TGFBI的表达与月经周期有所不同,在生殖阶段的水平更高,在分泌阶段的子宫外组织中表达更强.

结论:

缺氧诱导了在eutopic和ectopic子宫内膜层细胞中明显的转录组变化.
TGFBI被确定为子宫内膜异位症的潜在治疗点,因为它与纤维化和血管生成有关.

关键词:

美国联邦调查局TGFBI 子宫内膜异位症是什么?子宫内膜异位症是什么缺氧缺氧是指缺氧的情况.腹内膜病变的发生树皮细胞培养物中的细胞培养物翻译学翻译学翻译学翻译学

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