Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells.
Li-Ting Song, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Takahisa Imamura, Jan Potempa, Chang-Yi Li, Kenji Matsushita, Shunji Sugawara
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引用次数: 6
Abstract
Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.
纤溶酶原激活物抑制剂-1 (PAI-1)是一种丝氨酸蛋白酶抑制剂,由内皮细胞组成,在维持血管稳态中起重要作用。慢性牙周炎是一种以支持牙齿的牙周组织出血为特征的炎症性疾病。在这项研究中,我们旨在确定内皮细胞产生的PAI-1在对原发性牙周病原体牙龈卟啉单胞菌引起的感染的反应中的作用。我们证明牙龈假单胞菌感染导致人内皮细胞PAI-1水平显著降低。PAI-1水平的降低可能归因于牙龈卟啉卟啉蛋白酶对PAI-1的蛋白水解,特别是赖氨酸特异性gingipin - k (Kgp)。我们利用一种kp特异性抑制剂和牙龈卟啉卟啉缺失突变体证明了这些降解酶在内皮细胞中的作用,其中缺乏蛋白酶导致PAI-1降解缺失。牙龈假单胞菌对PAI-1的降解通过低密度脂蛋白受体相关蛋白在内皮细胞层诱导延迟伤口愈合反应。我们的研究结果表明,牙龈假单胞菌对内皮细胞中PAI-1的蛋白水解可能导致内皮稳态的失调,从而导致血管内皮屏障的通透性和功能障碍。
期刊介绍:
The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.