Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells.
Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells.
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DOI：
10.1159/000519737
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发表时间：
2022
影响因子：
5.3
通讯作者：
Sugawara, Shunji
中科院分区：
文献类型：
--
作者：
Song, Li-Ting;Tada, Hiroyuki;Nishioka, Takashi;Nemoto, Eiji;Imamura, Takahisa;Potempa, Jan;Li, Chang-Yi;Matsushita, Kenji;Sugawara, Shunji
纤溶酶原激活剂抑制剂-1 (PAI-1) 是一种丝氨酸蛋白酶抑制剂，由内皮细胞组成型产生，在维持血管稳态中发挥重要作用。慢性牙周炎是一种炎症性疾病，其特征是支撑牙齿的牙周组织出血。在本研究中，我们旨在确定内皮细胞产生的 PAI-1 在应对原发性牙周病原菌牙龈卟啉单胞菌引起的感染中的作用。我们证明牙龈卟啉单胞菌感染导致人内皮细胞中 PAI-1 水平显着降低。 PAI-1 水平的降低可能归因于牙龈卟啉单胞菌蛋白酶，特别是赖氨酸特异性牙龈蛋白酶-K (Kgp) 对 PAI-1 的蛋白水解。我们使用 Kgp 特异性抑制剂和 P. gingivalis gingipain-null 突变体证明了这些降解酶在内皮细胞中的作用，其中蛋白酶的缺乏导致 PAI-1 降解的缺失。牙龈卟啉单胞菌对 PAI-1 的降解通过低密度脂蛋白受体相关蛋白诱导内皮细胞层伤口愈合反应延迟。我们的结果总体表明，牙龈卟啉单胞菌牙龈蛋白酶对内皮细胞中 PAI-1 的蛋白水解可能导致内皮稳态失调，从而导致血管内皮屏障的通透性和功能障碍。
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.
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影响因子：
5.7
作者：
Ho MH;Guo ZM;Chunga J;Goodwin JS;Xie H
通讯作者：
Xie H
DOI：
10.1007/s003920050461
发表时间：
2000-03-01
期刊：
ZEITSCHRIFT FUR KARDIOLOGIE
影响因子：
--
作者：
Becker, BF;Heindl, B;Zahler, S
通讯作者：
Zahler, S
影响因子：
3.1
作者：
Dorn, BR;Dunn, WA;Progulske-Fox, A
通讯作者：
Progulske-Fox, A
影响因子：
18.6
作者：
Lewis JP
通讯作者：
Lewis JP
影响因子：
3.1
作者：
IMAMURA, T;POTEMPA, J;TRAVIS, J
通讯作者：
TRAVIS, J