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在复发性自发性流产中,CBLL1通过抑制PTEN促进子宫内膜 stromal 细胞衰老

Xueqing Liu^1,2,3, Xiaowei Wei^1,2,3, Jiayi Wu^1,2,3

¹The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

|July 16, 2024

概括

在决定体中增加的Cbl原型瘤基因像1 (CBLL1) 表达促进细胞衰老和氧化应激,导致复发性自发性流产 (RSA). 这一发现将CBLL1确定为RSA的潜在治疗标.

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
细胞和分子病理学的细胞和分子病理学.

背景情况:

复发性自发性流产 (RSA) 是一种常见的妊娠并发症,原因不明.
像1 (CBLL1) 这样的Cbl原瘤基因是一种E3泛素结合酶,在子宫内表现出依赖月经周期的表达.
目前尚不清楚CBLL1在RSA病变发生过程中的作用.

研究的目的:

研究CBLL1在复发性自发性流产中的表达和功能.
阐明CBLL1在RSA中的潜在作用背后的分子机制.
在人类子宫内膜层细胞 (HESCs) 中识别CBLL1的下游点.

主要方法:

在RSA患者和对照组的决定中分析CBLL1表达.
在体外对HESC进行研究,以评估CBLL1过度表达对衰老,氧化应激和增殖的影响.
RNA测序以识别CBLL1-调节的下游基因.
在体内小鼠模型中,评估子宫内膜CBLL1对胚胎吸收的影响.

主要成果:

在RSA患者的决定中,CBLL1表达显著上调.
在HESC中CBLL1的过度表达促进了细胞衰老,增加了氧化应激,并抑制了增殖.
酸酶和张素同源 (PTEN) 被确定为由CBLL1.1调节的关键下游向基因.
在体内实验表明,子宫内膜CBLL1表达升高导致小鼠的胚胎吸收率更高.

结论:

在决定的CBLL1表达的增加与反复的自发流产有关.
CBLL1通过诱导细胞衰老,氧化应激和子宫内膜功能受损来促进RSA的发病.
CBLL1代表了一种新的潜在治疗点,用于治疗复发性自发性流产.

关键词:

这就是CBLL1的意思.在这里,我们可以使用PTEN.细胞衰老细胞衰老胚胎内膜的 stromal 细胞.经常发生的自发性流产.

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