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牙龈卟啉单胞菌通过可溶性因子抑制滋养层细胞侵袭。

Porphyromonas gingivalis Suppresses Trophoblast Invasion by Soluble Factors.

机构信息

Department of Pathology and Microbiology, Division of Microbiology, Nihon University School of Medicine, Tokyo, Japan.

Department of Otolaryngology Head and Neck Surgery, Division of Oral Surgery, Nihon University School of Medicine.

出版信息

J Periodontol. 2017 Dec;88(12):1366-1373. doi: 10.1902/jop.2017.170193. Epub 2017 Jul 28.

Abstract

BACKGROUND

Periodontitis is a common chronic inflammatory disorder that affects supporting tissues of the teeth. An increased risk of pregnancy complications has been reported in patients with periodontitis; however, its pathophysiology remains uncharacterized to date. In addition, Porphyromonas gingivalis (Pg) is detectable in a few placentae derived from diseased pregnancies. Thus, the aim of this study is to examine the roles of soluble factors produced by Pg on trophoblast invasion in vitro to clarify the remote effects of periodontitis on pregnancy outcomes.

METHODS

The immortalized trophoblast cell line HTR-8/SVneo was cultured on plates or via hanging drop to evaluate viability, apoptosis, and morphology in the presence of the culture supernatant of Pg (PG-sup). Cells were plated on solubilized extracellular matrix rich membrane preparation plates to evaluate cell invasion. Morphologic changes were evaluated via stereomicroscopy, optical microscopy, and transmission electron microscopy.

RESULTS

After 24 hours of culture, cell invasion was inhibited by PG-sup in a dose-dependent manner. Although cell viability and apoptotic counts were not affected by PG-sup, spheroid formation in hanging drop culture was inhibited. Spheroids became fragile and irregular in the presence of PG-sup. Transmission electron microscopy revealed shortened microvilli and increased intracellular spaces.

CONCLUSIONS

PG-sup inhibits trophoblast invasion and affects trophoblast morphology without direct cytotoxicity. These results indicate that Pg produces soluble factor(s) that suppress trophoblast invasion and subsequent vascular remodeling, which affect placental growth and fetal well-being. It is expected that the current findings will explain the increased prevalence of pregnancy complications in patients with periodontitis.

摘要

背景

牙周炎是一种常见的慢性炎症性疾病,影响牙齿的支持组织。患有牙周炎的患者患妊娠并发症的风险增加,但迄今为止其病理生理学仍未得到描述。此外,牙龈卟啉单胞菌(Pg)可在一些源自患病妊娠的胎盘上检测到。因此,本研究旨在研究 Pg 产生的可溶性因子对体外滋养细胞侵袭的作用,以阐明牙周炎对妊娠结局的远程影响。

方法

将永生化的滋养层细胞系 HTR-8/SVneo 培养在平板上或通过悬滴培养,以评估 Pg 培养上清液(PG-sup)存在时的细胞活力、细胞凋亡和形态。将细胞接种在富含细胞外基质的可溶性膜制备板上,以评估细胞侵袭。通过立体显微镜、光学显微镜和透射电子显微镜评估形态变化。

结果

培养 24 小时后,PG-sup 以剂量依赖性方式抑制细胞侵袭。尽管 PG-sup 不影响细胞活力和细胞凋亡计数,但悬滴培养中的球体形成受到抑制。在 PG-sup 存在下,球体变得脆弱且不规则。透射电子显微镜显示微绒毛缩短和细胞内空间增加。

结论

PG-sup 抑制滋养细胞侵袭并影响滋养细胞形态,而没有直接的细胞毒性。这些结果表明,Pg 产生抑制滋养细胞侵袭和随后的血管重塑的可溶性因子,从而影响胎盘生长和胎儿健康。预计目前的研究结果将解释牙周炎患者妊娠并发症发生率增加的原因。

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