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

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...

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Autores principales:	Li-Ting Song, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Takahisa Imamura, Jan Potempa, Chang-Yi Li, Kenji Matsushita, Shunji Sugawara
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	bacterial infection endothelial cells pathogenesis wound healing periodontitis Medicine R Internal medicine RC31-1245
Acceso en línea:	https://doaj.org/article/e05f9995576f4bf796da5ebd26b89ef9
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spelling	oai:doaj.org-article:e05f9995576f4bf796da5ebd26b89ef92021-12-02T12:40:22ZPorphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells1662-811X1662-812810.1159/000519737https://doaj.org/article/e05f9995576f4bf796da5ebd26b89ef92021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/519737https://doaj.org/toc/1662-811Xhttps://doaj.org/toc/1662-8128Plasminogen 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.Li-Ting SongHiroyuki TadaTakashi NishiokaEiji NemotoTakahisa ImamuraJan PotempaChang-Yi LiKenji MatsushitaShunji SugawaraKarger Publishersarticlebacterial infectionendothelial cellspathogenesiswound healingperiodontitisMedicineRInternal medicineRC31-1245ENJournal of Innate Immunity, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial infection endothelial cells pathogenesis wound healing periodontitis Medicine R Internal medicine RC31-1245
spellingShingle	bacterial infection endothelial cells pathogenesis wound healing periodontitis Medicine R Internal medicine RC31-1245 Li-Ting Song Hiroyuki Tada Takashi Nishioka Eiji Nemoto Takahisa Imamura Jan Potempa Chang-Yi Li Kenji Matsushita Shunji Sugawara Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells
description	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.
format	article
author	Li-Ting Song Hiroyuki Tada Takashi Nishioka Eiji Nemoto Takahisa Imamura Jan Potempa Chang-Yi Li Kenji Matsushita Shunji Sugawara
author_facet	Li-Ting Song Hiroyuki Tada Takashi Nishioka Eiji Nemoto Takahisa Imamura Jan Potempa Chang-Yi Li Kenji Matsushita Shunji Sugawara
author_sort	Li-Ting Song
title	Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells
title_short	Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells
title_full	Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells
title_fullStr	Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells
title_full_unstemmed	Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells
title_sort	porphyromonas gingivalis gingipains-mediated degradation of plasminogen activator inhibitor-1 leads to delayed wound healing responses in human endothelial cells
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/e05f9995576f4bf796da5ebd26b89ef9
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Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells

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