Porphyromonas gingivalis outer membrane vesicles exacerbate retinal microvascular endothelial cell dysfunction in diabetic retinopathy.
Porphyromonas gingivalis outer membrane vesicles exacerbate retinal microvascular endothelial cell dysfunction in diabetic retinopathy.
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DOI：
10.3389/fmicb.2023.1167160
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发表时间：
2023
影响因子：
5.2
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中科院分区：
文献类型：
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糖尿病视网膜病变（DR）是导致失明的主要原因之一。牙周炎是口腔发病率最高的疾病之一，通过牙龈卟啉单胞菌（P. gingivalis）与各种全身疾病密切相关。牙龈假单胞菌omv来源于牙龈假单胞菌，可引起内皮功能障碍并可能影响微血管疾病。目前的流行病学研究提供了有限的证据表明牙周炎与DR相关，但缺乏关于牙周炎如何影响DR严重程度的基础研究。本研究旨在探讨牙龈假单胞菌omv在DR发病机制中的潜在作用，并探讨其如何影响视网膜微血管内皮。结果表明，牙龈假单胞菌omv加速了DR小鼠血视网膜屏障的损伤。体外研究表明，牙龈假单胞菌omv刺激后，人视网膜微血管内皮细胞（HRMECs）炎症因子表达增加，HRMECs活性氧产生增加，线粒体功能障碍，细胞凋亡，内皮通透性改变。此外，我们发现蛋白酶活化受体2 （PAR-2）调节omvs诱导的TNF-α、MMP-9 mRNA表达、细胞死亡和内皮通透性。总之，我们认为牙龈假单胞菌omv诱导HRMECs线粒体相关细胞死亡，加速内皮功能障碍，从而加重DR，其中PAR-2可能起潜在作用。本研究首次阐述了牙龈卟啉卟啉单胞菌omv在DR发病机制中的潜在分子机制，独特地阐明了牙周病原体衍生物对DR进展的可能影响。
Diabetic retinopathy (DR) is one of the leading causes of blindness. Periodontitis is one of the highest oral incidences and has been closely related to various systemic conditions through Porphyromonas gingivalis (P. gingivalis). P. gingivalis OMVs, derived from P. gingivalis, can cause endothelial dysfunction and potentially affect microvascular diseases. Current epidemiological studies provide limited evidence suggesting that periodontitis is associated with DR. However, there is a lack of basic research elucidating how periodontitis affects the severity of DR. This study aimed to explore the potential of P. gingivalis OMVs to contribute to the pathogenesis of DR and explore how it affect the retinal microvascular endothelium. The results demonstrated that P. gingivalis OMVs accelerated the blood-retinal barrier damage in DR mice. In vitro studies showed that the expression of inflammatory factors in human retinal microvascular endothelial cells (HRMECs) was increased after P. gingivalis OMVs stimulation, and the increased reactive oxygen species production, mitochondrial dysfunction, apoptosis, and altered endothelial permeability were observed in HRMECs under P. gingivalis OMVs stimulation. In addition, we found that protease-activated receptor-2 (PAR-2) regulated OMVs-induced TNF-α, MMP-9 mRNA expression, cell death, and endothelial permeability. Overall, we suggested that P. gingivalis OMVs induced mitochondria-related cell death of HRMECs and accelerated endothelial dysfunction, thus aggravating DR, in which PAR-2 plays a potential role. This study is the first research report to delineate the potential molecular mechanism of P. gingivalis OMVs on DR pathogenesis, which uniquely focused on elucidating the possible impact of periodontal pathogen derivatives on DR progression.