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DJ-1 下调对孕早期绒毛外滋养层细胞功能的影响。

Effect of DJ-1 Downregulation on the Functions of the First Trimester Extravillous Trophoblasts.

作者信息

Kwon Han-Sung, Park Ji Hyun, Hwang Han-Sung, Sohn In-Sook, Kim Young-Han, Cho SiHyun

机构信息

1 Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea.

2 Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Reprod Sci. 2018 Sep;25(9):1436-1445. doi: 10.1177/1933719117746760. Epub 2017 Dec 19.

Abstract

DJ-1 ( PARK7) has been reported to be causative gene of Parkinson disease and also an oncogene. A loss in DJ-1 function can lead to cell death in neurodegenerative disease, or a gain of it can cause unregulated cell survival in cancer, respectively. DJ-1 protein is known to be expressed mainly in trophoblastic cells in the placenta with increased expression in the first trimester compared to later in term. However, its role in trophoblast regulation remains unknown. This study aimed to investigate the effect of DJ-1 regulation on a first trimester extravillous trophoblast cell line, HTR-8/SVneo. The effect of DJ-1 downregulation induced by small-interfering RNA on cell apoptosis, migration, and the pathway to regulate the cell function was assessed. Data of this study showed that DJ-1 downregulation increased apoptosis and reduced migration by regulating matrix metalloproteinase 2 and matrix metalloproteinase 9 in HTR-8/SVneo cells under both ambient and oxidative stress. Changes in cell function were demonstrated to be at least partly dependent on the AKT/S6 kinase beta-1 (S6K1) pathway. In summary, DJ-1 might play a protective role in maintaining trophoblastic cell functions through the AKT/S6K1-based pathway.

摘要

DJ-1(PARK7)已被报道为帕金森病的致病基因,也是一种癌基因。DJ-1功能丧失可导致神经退行性疾病中的细胞死亡,而其功能获得则可分别导致癌症中细胞的异常存活。已知DJ-1蛋白主要在胎盘的滋养层细胞中表达,与孕晚期相比,在孕早期表达增加。然而,其在滋养层调节中的作用仍不清楚。本研究旨在探讨DJ-1调节对早孕期绒毛外滋养层细胞系HTR-8/SVneo的影响。评估了小干扰RNA诱导的DJ-1下调对细胞凋亡、迁移以及调节细胞功能途径的影响。本研究数据表明,在环境应激和氧化应激下,DJ-1下调通过调节HTR-8/SVneo细胞中的基质金属蛋白酶2和基质金属蛋白酶9增加细胞凋亡并减少细胞迁移。细胞功能的变化被证明至少部分依赖于AKT/ S6激酶β-1(S6K1)途径。总之,DJ-1可能通过基于AKT/S6K1的途径在维持滋养层细胞功能中发挥保护作用。

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