Porphyromonas gingivalis invades human trophoblasts and inhibits proliferation by inducing G1 arrest and apoptosis.
Porphyromonas gingivalis invades human trophoblasts and inhibits proliferation by inducing G1 arrest and apoptosis.
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牙龈卟啉单胞菌侵入人类滋养细胞，并通过诱导G1停滞和凋亡抑制增殖。
DOI：
10.1111/j.1462-5822.2009.01344.x
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发表时间：
2009-10
影响因子：
3.4
通讯作者：
Lamont RJ
中科院分区：
文献类型：
--
作者：
Inaba H;Kuboniwa M;Bainbridge B;Yilmaz O;Katz J;Shiverick KT;Amano A;Lamont RJ
牙龈卟啉单胞菌是一种口腔病原体，也与严重的全身性疾病如早产有关。在这里，我们研究了牙龈卟啉单胞菌和绒毛外滋养层细胞（HTR-8）来自人胎盘的细胞系之间的相互作用。牙龈卟啉单胞菌内化在HTR-8细胞内，并通过诱导细胞周期的G1期停滞来抑制增殖。G1期阻滞与细胞周期蛋白D和CDKs 2、4和6的表达降低相关。此外，牙龈卟啉单胞菌感染后，CDK抑制剂p15、p16、p18和p21的水平增加。牙龈卟啉单胞菌减少了Rb的量，Rb的瞬时过表达，伴随着磷酸化Rb的上调，减轻了牙龈卟啉单胞菌诱导的G1期阻滞。HTR-8细胞停止在G1期成为凋亡，凋亡伴随着Bax/Bcl-2的比例增加和caspase 3，7和9的活性增加。感染牙龈卟啉单胞菌的HTR-8细胞也表现出ERK 1/2的持续激活，并且用siRNA敲低ERK 1/2活性消除了G1停滞和凋亡。因此，牙龈卟啉单胞菌可以侵入胎盘滋养层细胞，并通过涉及ERK 1/2及其下游效应物的途径诱导G1期阻滞和细胞凋亡，这些特性为妊娠并发症的致病性提供了机制基础。
Porphyromonas gingivalis is an oral pathogen that is also associated with serious systemic conditions such as preterm delivery. Here we investigated the interaction between P. gingivalis and a cell line of extravillous trophoblasts (HTR-8) derived from the human placenta. P. gingivalis internalized within HTR-8 cells and inhibited proliferation through induction of arrest in the G1 phase of the cell cycle. G1 arrest was associated with decreased expression of cyclin D and of CDKs 2, 4 and 6. In addition, levels of CDK inhibitors p15, p16, p18 and p21 were increased following P. gingivalis infection. The amount of Rb was diminished by P. gingivalis, and transient overexpression of Rb, with concomitant upregulation of phospho-Rb, relieved P. gingivalis-induced G1 arrest. HTR-8 cells halted in the G1 phase became apoptotic, and apoptosis was accompanied by an increase in the ratio of Bax/Bcl-2 and increased activity of caspases 3, 7 and 9. HTR-8 cells infected with P. gingivalis also exhibited a sustained activation of ERK1/2, and knockdown of ERK1/2 activity with siRNA abrogated both G1 arrest and apoptosis. Thus, P. gingivalis can invade placental trophoblasts and induce G1 arrest and apoptosis through pathways involving ERK1/2 and its downstream effectors, properties that provide a mechanistic basis for pathogenicity in complications of pregnancy.
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影响因子：
3.4
作者：
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通讯作者：
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