Liang Yue, Wang Ping, Shi Yueyang, Cui Bihong, Meng Jinlai
Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Front Mol Biosci. 2022 Oct 14;9:1022450. doi: 10.3389/fmolb.2022.1022450. eCollection 2022.
Inadequate trophoblastic infiltration and resulting placental hypoxia and inflammation comprise the core pathological basis of preeclampsia (PE). Maternally expressed gene 3 () is known to be involved in the pathogenesis of preeclampsia by inhibiting the migration and invasion of trophoblasts and promoting their apoptosis. Nevertheless, the specific underlying downstream molecular mechanism of is less well characterized. In this study, we detected lower expression levels of and -Catenin and higher expression of nod-like receptor pyrin domain-containing 3 (NLRP3) in placental tissues of pregnant women with severe preeclampsia (sPE) than in normal pregnancies. Elevated serum levels of IL-1β and TNF-α were also observed in the sPE group. Then, we established a hypoxia/reoxygenation (H/R) model to mimic preeclampsia. Similar results with sPE group were found in the H/R group compared with the control group. In addition, suppressive trophoblast proliferation, migration and invasion and increases in the apoptotic rate and inflammation were also detected in the H/R group. Notably, overexpressing markedly improved trophoblast dysfunction and inflammation caused by H/R. However, the effects of on trophoblasts, whether upregulated or downregulated, can be reversed by DKK-1 (Wnt/-Catenin inhibitor) and MCC950 (NLRP3 inhibitor). The current study revealed that regulates trophoblast function and inflammation through the Wnt/-Catenin/NLRP3 axis and provided new insights into the pathogenesis of preeclampsia.
滋养层细胞浸润不足以及由此导致的胎盘缺氧和炎症构成了子痫前期（PE）的核心病理基础。已知母源表达基因3（）通过抑制滋养层细胞的迁移和侵袭并促进其凋亡而参与子痫前期的发病机制。然而，其具体的潜在下游分子机制尚不清楚。在本研究中，我们检测到重度子痫前期（sPE）孕妇胎盘组织中 和 -连环蛋白的表达水平低于正常妊娠，而含核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）的表达水平高于正常妊娠。sPE组血清白细胞介素-1β和肿瘤坏死因子-α水平也升高。然后，我们建立了缺氧/复氧（H/R）模型来模拟子痫前期。与对照组相比，H/R组出现了与sPE组相似的结果。此外，在H/R组中还检测到滋养层细胞增殖、迁移和侵袭受到抑制，凋亡率和炎症增加。值得注意的是，过表达 显著改善了H/R引起的滋养层细胞功能障碍和炎症。然而，无论 上调还是下调，其对滋养层细胞的影响均可被DKK-1（Wnt/-连环蛋白抑制剂）和MCC950（NLRP3抑制剂）逆转。本研究揭示了 通过Wnt/-连环蛋白/NLRP3轴调节滋养层细胞功能和炎症，为子痫前期的发病机制提供了新的见解。
