Department of Perinatology, Gynecology and Gynecologic Oncology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Łukasiewicza 1, 85-821 Bydgoszcz, Poland.
Department of Obstetrics and Gynecology, St. Adalbert's Hospital in Gdańsk, Copernicus Healthcare Entity, Jana Pawła II 50, 80-462 Gdańsk, Poland.
Int J Mol Sci. 2021 Jan 12;22(2):704. doi: 10.3390/ijms22020704.
Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide. It afflicts 2-8% of pregnancies and is the most common cause of gestational hypertension. This article is focused on nuclear factor kappa B (NF-κB), its role in normal and pathological spiral arteries remodelling and development of preeclampsia, with evaluation if it is a promising therapeutic target. NF-κB is a key mediator of placentation. Since insemination, it stimulates production of proinflammatory cytokines by the uterine epithelium, which leads to activation of macrophages, uterine natural killer cells (uNKs), and other leukocytes. The trophoblast/uNK/macrophage crosstalk is crucial for implantation and spiral arteries remodeling, and NF-κB regulates that process through modification of cytokine expression, as well as cell phenotype and function. In the course of preeclampsia, the remodeling processes is disturbed by excessive inflammation and increased NF-κB activation. The pathological remodeling leads to uteroplacental dysfunction, release of proinflammatory cytokines into the maternal circulation, endothelial stress, and development of preeclampsia. The analysis of genetic and environmental inductors of NF-κB helps to distinguish preeclampsia risk groups. Furthermore, a selective inhibition of NF-κB or NF-κB activating pathways alleviates symptoms of preeclampsia in rat models; therefore, this could be an efficient therapeutic option.
子痫前期是全球孕产妇发病率和死亡率的三大主要原因之一。它影响 2-8%的妊娠，是妊娠高血压最常见的原因。本文重点介绍核因子 kappa B（NF-κB），它在正常和病理性螺旋动脉重塑以及子痫前期发展中的作用，并评估其是否是一个有前途的治疗靶点。NF-κB 是胎盘形成的关键介质。自授精以来，它刺激子宫上皮细胞产生促炎细胞因子，导致巨噬细胞、子宫自然杀伤细胞（uNK）和其他白细胞的激活。滋养层/uNK/巨噬细胞相互作用对于着床和螺旋动脉重塑至关重要，NF-κB 通过调节细胞因子表达、细胞表型和功能来调节该过程。在子痫前期过程中，重塑过程受到过度炎症和 NF-κB 激活增加的干扰。病理性重塑导致胎盘功能障碍，促炎细胞因子释放到母体循环中，内皮应激，以及子痫前期的发展。对 NF-κB 的遗传和环境诱导因素的分析有助于区分子痫前期的风险群体。此外，选择性抑制 NF-κB 或 NF-κB 激活途径可减轻子痫前期大鼠模型的症状；因此，这可能是一种有效的治疗选择。
