Nox4 mediates the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells

2009 ◽  
Vol 124 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Amandine Jaulmes ◽  
Patricia Sansilvestri-Morel ◽  
Gaëlle Rolland-Valognes ◽  
Fabienne Bernhardt ◽  
Roger Gaertner ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Plasminogen Activator Inhibitor ◽  
Human Endothelial Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
P38 Mapk Pathway ◽  
Activator Inhibitor

scholarly journals Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells

2021 ◽  
pp. 1-14
Author(s):  
Li-Ting Song ◽  
Hiroyuki Tada ◽  
Takashi Nishioka ◽  
Eiji Nemoto ◽  
Takahisa Imamura ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Porphyromonas Gingivalis ◽  
Plasminogen Activator Inhibitor ◽  
Human Endothelial Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
Delayed Wound Healing ◽  
Activator Inhibitor ◽  
Pai 1

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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