The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia

International Journal of Molecular Sciences

Oskar Puk¹  Anita Kazdepka-Ziemińska¹  MaciejW. Socha¹  Mateusz Wartęga¹  Martyna Stankiewicz¹  Michał Wiciński²  Bartosz Malinowski² 

[1] 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 Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland;

关键词: nuclear factor kappa B;    preeclampsia;    pregnancy;    inflammation;    pathway;    trophoblast;   

DOI  :  10.3390/ijms22020704

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown