FAK信号在人类妊娠早期胎盘发育和滋养细胞谱系分化中的作用

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-06-18 DOI:10.1016/j.cellsig.2025.111946

Hong-Xiu Liang , Cen Yi , Si-Hui He , Li-Yang Zhou , Fang-Fang Li , Jing Tang , En-Xiang Chen , Li-Juan Fu , Ying-Xiong Wang , You-Long Xie , Yu-Bin Ding

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引用次数: 0

摘要

胎盘是母胎交换的重要界面，依靠滋养细胞分化发育。这一过程包括细胞滋养层细胞（CTBs）向合胞滋养层细胞（STBs）和胞外滋养层细胞（EVTs）过渡，推动胎盘成熟。局灶黏附激酶（FAK）是一种关键的细胞质酪氨酸激酶，调节细胞增殖、存活和信号传导等过程。然而，其在滋养细胞分化和代谢中的作用尚不清楚。本研究利用人滋养细胞干细胞（hTSCs）和滋养细胞系（BeWo, HTR8/SVneo），研究了FAK信号在滋养细胞谱系分化中的作用。抑制FAK信号通路可抑制MAPK通路活性，降低糖酵解代谢，损害滋养细胞合胞。此外，用抑制剂Defactinib阻断FAK会破坏evt的细胞骨架，损害其迁移、侵袭和分化潜能。值得注意的是，在复发性自然流产（RSA）患者中观察到FAK信号的减少，这表明FAK信号在RSA发病机制中起作用。我们的研究结果强调FAK是滋养细胞谱系发育的关键调节因子，将其与胎盘功能和RSA联系起来。这项研究为胎盘疾病和潜在的治疗靶点提供了新的见解。

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The role of FAK signaling in early placental development and trophoblast lineage specification in human pregnancy

The placenta serves as a vital interface for fetal-maternal exchange, relying on trophoblast differentiation for development. This process involves cytotrophoblasts (CTBs) transitioning into syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs), driving placental maturation. Focal adhesion kinase (FAK), a key cytoplasmic tyrosine kinase, regulates cellular processes such as proliferation, survival, and signaling. However, its role in trophoblast differentiation and metabolism remains unclear. Here, using human trophoblast stem cells (hTSCs) and trophoblast cell lines (BeWo, HTR8/SVneo), we investigated FAK signaling in trophoblast lineage differentiation. Inhibiting the FAK signaling pathway suppresses MAPK pathway activity, reduces glycolytic metabolism and impairs trophoblast syncytialization. Additionally, blocking FAK with the inhibitor Defactinib disrupts EVTs cytoskeleton and impairs migration, invasion, and differentiation potential. Notably, reduced FAK signaling is observed in patients with recurrent spontaneous abortion (RSA), suggesting a role in RSA pathogenesis. Our findings highlight FAK as a pivotal regulator of trophoblast lineage development, linking it to placental function and RSA. This study offers new insights into placental disorders and potential therapeutic targets.

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.