{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:36:00Z","timestamp":1791945360041,"version":"4.3.4"},"reference-count":54,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>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 &lt;i&gt;Porphyromonas gingivalis&lt;\/i&gt;. We demonstrated that &lt;i&gt;P. gingivalis&lt;\/i&gt; 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 &lt;i&gt;P. gingivalis&lt;\/i&gt; 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 &lt;i&gt;P. gingivalis&lt;\/i&gt; gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by &lt;i&gt;P. gingivalis&lt;\/i&gt; 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 &lt;i&gt;P. gingivalis&lt;\/i&gt; might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier. <\/jats:p>","DOI":"10.1159\/000519737","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T07:31:21Z","timestamp":1639035081000},"page":"306-319","source":"Crossref","is-referenced-by-count":24,"title":["&lt;b&gt;&lt;i&gt;Porphyromonas gingivalis&lt;\/i&gt;&lt;\/b&gt; Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial 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