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探讨晚期子痫前期胎盘中自噬标志物差异表达的重要性。

Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies.

机构信息

Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.

Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

出版信息

Int J Mol Sci. 2024 Feb 7;25(4):2029. doi: 10.3390/ijms25042029.

Abstract

Preeclampsia (PE) is a serious hypertensive disorder affecting 4-5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE ( = 68) and compared them to normal pregnancies ( = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

摘要

子痫前期 (PE) 是一种严重的高血压疾病,影响全球 4-5%的妊娠,导致母婴围产期发病率和死亡率增加,并降低妊娠后幸存妇女的预期寿命。晚发型子痫前期 (LO-PE) 是一种在妊娠 34 周后诊断的临床类型的子痫前期,其严重程度低于早发型子痫前期 (EO-PE) 变异型,尽管两者都对胎盘有显著影响。尽管大多数研究都集中在 EO-PE 上,但 LO-PE 不应受到较少关注,因为它的患病率高得多,而且对这种病理中胎盘的作用知之甚少。通过 RT-qPCR 和免疫组织化学方法,我们测量了胎盘绒毛中几种巨自噬标志物的基因和蛋白表达,将其与正常妊娠进行了比较(n=43)。我们观察到明显不同的表达模式,注意到 NUP62 的表达显著下降,而 ULK1、ATG9A、LC3、ATG5、STX-17 和 LAMP-1 的基因和蛋白表达在 LO-PE 患者的胎盘显著增加。在 LO-PE 患者的胎盘组织中发现了自噬过程的主要诱导。这些分子模式在这种情况下异常信号表达有助于理解病理生理学的复杂性,并为这些患者的临床管理提出了生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e5/10888358/f87724a48733/ijms-25-02029-g001.jpg

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