2. Academic Validation
  3. 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

  • J Innate Immun. 2022;14(4):306-319. doi: 10.1159/000519737.
Li-Ting Song 1 2,  Hiroyuki Tada 1,  Takashi Nishioka 3,  Eiji Nemoto 4,  Takahisa Imamura 5,  Jan Potempa 6 7,  Chang-Yi Li 2,  Kenji Matsushita 8,  Shunji Sugawara 1
Affiliations

Affiliations

  • 1 Division of Oral Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
  • 2 Hospital of Stomatology, School of Dentistry, Tianjin Medical University, Tianjin, China.
  • 3 Division of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai, Japan.
  • 4 Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
  • 5 Department of Nutritional Science, Faculty of Human Life Science, Shokei University, Kumamoto, Japan.
  • 6 Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Kraków, Poland.
  • 7 Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA.
  • 8 Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan.
PMID: 34823251 DOI: 10.1159/000519737
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.

Keywords

Bacterial infection; Endothelial cells; Pathogenesis; Periodontitis; Wound healing.

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