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短暂和持续激活 Wnt 信号对 Asherman 综合征的发病机制有相反的作用。

Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman's Syndrome.

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

Int J Mol Sci. 2022 Aug 8;23(15):8808. doi: 10.3390/ijms23158808.

DOI:10.3390/ijms23158808
PMID:35955940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9368949/
Abstract

Asherman's Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated β-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140bCD146 endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/β-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/β-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/β-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation.

摘要

Asherman 综合征(AS)是由子宫内膜再生能力障碍引起的,其受成体干细胞及其龛位调控。Wnt 信号通路已被证实参与这一过程。本研究旨在阐明 Wnt 信号通路与初始子宫内膜损伤后 AS 进展之间的关系。收集有粘连和无粘连的子宫内膜以及手术后三个月的宫内节育器,以比较纤维化面积。纤维化面积百分比无显著差异。粘连子宫内膜中存在非磷酸化β-连环蛋白、Wnt5a 和 Wnt7a 的高表达。黏附的子宫内膜中有 CD140bCD146 子宫内膜干细胞样细胞。Wnt5a 和 Wnt7a 均可促进干细胞增殖,但只有 Wnt7a 通过刺激自我更新来维持干细胞群体。建立大鼠子宫内膜损伤模型,研究激活的 Wnt/β-连环蛋白信号通路对子宫内膜愈合的影响。我们发现,Wnt/β-连环蛋白信号通路的短暂激活促进了血管生成并增加了腺体数量。总之,急性子宫内膜损伤期间 Wnt/β-连环蛋白信号通路的短暂激活可能有助于组织再生,而持续激活可能与纤维化形成相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8700/9368949/188b13fd5d30/ijms-23-08808-g005.jpg
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Single-cell RNA sequencing of cultured human endometrial CD140bCD146 perivascular cells highlights the importance of in vivo microenvironment.对培养的人子宫内膜 CD140bCD146 血管周细胞的单细胞 RNA 测序强调了体内微环境的重要性。
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