转化生长因子-β超家族在子痫前期发病机制中的作用

doi:10.12280/gjfckx.20240917

摘要/Abstract

摘要：

子痫前期（preeclampsia，PE）是一种妊娠期特有的疾病，胎盘滋养细胞侵袭不足和螺旋动脉重塑受损可能是关键因素。转化生长因子-β（transforming growth factor-β，TGF-β）超家族成员通过激活跨膜丝氨酸/苏氨酸激酶受体，触发下游信号传导，影响胎盘滋养细胞侵袭、免疫功能、血管生成及炎症反应等关键环节。骨形态发生蛋白（bone morphogenetic protein，BMP）亚家族成员（如BMP2）通过影响滋养细胞的分化与侵袭、调节巨噬细胞的极化状态以及调控TGF-β超家族其他成员的表达，抑制PE的发生发展；BMP7可以促进滋养细胞钙化，进而导致胎盘血管发育不良；BMP9可以调节基质金属蛋白酶（matrix metalloproteinase，MMP）的表达促进滋养细胞迁移和侵袭；BMP11可以通过抑制核因子κB（nuclear factor-κB，NF-κB）信号通路的激活、活性氧的产生及炎症因子的表达，发挥抗炎作用，但其在PE中具体作用尚存争议。生长分化因子（growth and differentiation factor，GDF）亚家族成员（如GDF-8和GDF-15）主要通过调控MMP的表达及上皮-间充质转化影响滋养细胞的侵袭，此外GDF-15还可能通过抑制NF-κB信号通路并减少促炎细胞因子的表达，发挥抗炎作用。激活素通过调节MMP和整合素β1的表达，影响滋养细胞的侵袭和增殖，还可能导致内皮细胞功能障碍，从而参与PE的病理过程；而抑制素则在预测PE方面具有潜在应用价值。多项研究已证实TGF-β超家族成员与PE的发生发展密切相关，但具体调控机制仍需进一步探讨，以寻找潜在的治疗靶点和预测PE发生的生物学标志物。

关键词: 先兆子痫, TGFβ超家族蛋白质类, 骨形态发生蛋白质类, 生长分化因子类, 抑制素类, 激活素类

Abstract:

Preeclampsia (PE) is a pregnancy-specific disorder characterized by inadequate trophoblast invasion and impaired spiral artery remodeling. Members of the transforming growth factor-β (TGF-β) superfamily, through activation of transmembrane serine/threonine kinase receptors and subsequent downstream signaling, influence key processes in PE pathogenesis, including trophoblast invasion, immune function, angiogenesis, and inflammation. Bone morphogenetic protein (BMP) subfamily members, such as BMP2, inhibit PE development by influencing trophoblast differentiation and invasion, modulating macrophage polarization, and regulating the expression of other TGF-β superfamily members. BMP7 promotes trophoblast calcification, potentially leading to placental vascular dysfunction. BMP9 promotes trophoblast migration and invasion by regulating matrix metalloproteinase (MMP) expression. BMP11 exerts anti-inflammatory effects by inhibiting nuclear factor-κB (NF-κB) signaling pathway activation, reactive oxygen species production, and inflammatory cytokine expression; However, its precise role in PE remains controversial. Growth and differentiation factor (GDF) subfamily members, such as GDF-8 and GDF-15, primarily affect trophoblast invasion by modulating MMP expression and epithelial-mesenchymal transition (EMT). GDF-15 may also exert anti-inflammatory effects by suppressing NF-κB signaling and reducing pro-inflammatory cytokines expression. Activins influence trophoblast invasion and proliferation by regulating MMP and integrin β1 expression and may contribute to PE pathogenesis by causing endothelial dysfunction. In contrast, inhibins show potential as predictors of PE. Numerous studies have confirmed the close association between TGF-β superfamily members and the development of PE; however, the precise regulatory mechanisms require further investigation to identify potential therapeutic targets and biomarkers for PE prediction.

Key words: Pre-eclampsia, TGF-beta superfamily proteins, Bone morphogenetic proteins, Growth differentiation factors, Inhibins, Activins

王一丹, 王永红. 转化生长因子-β超家族在子痫前期发病机制中的作用[J]. 国际妇产科学杂志, 2025, 52(1): 99-104.

WANG Yi-dan, WANG Yong-hong. The Role of the Transforming Growth Factor-β Superfamily in the Pathogenesis of Preeclampsia[J]. Journal of International Obstetrics and Gynecology, 2025, 52(1): 99-104.

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