Mechanisms of Tissue Factor Induction by Porphyromonas gingivalis in Human Endothelial Cells
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Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis . Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms. solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.
Abstract
Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis . Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms. solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.
참고문헌 (25)
- Kinane DF, "Periodontal diseases", Nat Rev Dis Primers, 3, pp.17038~ (2017)[DOI]
- Könönen E, "Periodontitis : a multifaceted disease of tooth-supporting tissues", J Clin Med, 8, pp.1135~ (2019)[DOI]
- Bui FQ, "Association between periodontal pathogens and systemic disease", Biomed J, 42, pp.27~35 (2019)[DOI]
- Hasturk H, "Activation and resolution of periodontal inflammation and its systemic impact", Periodontol 2000, 69, pp.255~273 (2015)[DOI]
- Mulhall H, "Porphyromonas gingivalis, a longrange pathogen: systemic impact and therapeutic implications", Microorganisms, 8, pp.869~ (2020)[DOI]
- Xu W, "Roles of Porphyromonas gingivalis and its virulence factors in periodontitis", Adv Protein Chem Struct Biol, 120, pp.45~84 (2020)[DOI]
- Haraszthy VI, "Identification of periodontal pathogens in atheromatous plaques", J Periodontol, 71, pp.1554~1560 (2000)[DOI]
- Kozarov EV, "Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis", Arterioscler Thromb Vasc Biol, 25, pp.e17~8 (2005)[DOI]
- Olsen I, "Invasion of Porphyromonas gingivalis strains into vascular cells and tissue", J Oral Microbiol, 7, pp.28788~ (2015)[DOI]
- Lalla E, "Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice", Arterioscler Thromb Vasc Biol, 23, pp.1405~1411 (2003)[DOI]
- Pussinen PJ, "Periodontal infections and atherosclerosis : mere associations", Curr Opin Lipidol, 15, pp.583~588 (2004)[DOI]
- Grover SP, "Tissue factor : an essential mediator of hemostasis and trigger of thrombosis", Arterioscler Thromb Vasc Biol, 38, pp.709~725 (2018)[DOI]
- Steffel J, "Tissue factor in cardiovascular diseases : molecular mechanisms and clinical implications", Circulation, 113, pp.722~731 (2006)[DOI]
- Witkowski M, "Tissue factor as a link between inflammation and coagulation", Trends Cardiovasc Med, 26, pp.297~303 (2016)[DOI]
- Roth GA, "Porphyromonas gingivalis infection and prothrombotic effects in human aortic smooth muscle cells", Thromb Res, 123, pp.780~784 (2009)[DOI]
- Roth GA, "Infection with a periodontal pathogen induces procoagulant effects in human aortic endothelial cells", J Thromb Haemost, 4, pp.2256~2261 (2006)[DOI]
- Gavrilin MA, "Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release", Proc Natl Acad Sci U S A, 103, pp.141~146 (2006)[DOI]
- Kang IC, "Induction of monocyte chemoattractant protein-1 by Porphyromonas gingivalis in human endothelial cells", FEMS Immunol Med Microbiol, 34, pp.311~317 (2002)[DOI]
- Shin OS, "Distinct roles for MyD88 and Toll-like receptors 2, 5, and 9 in phagocytosis of Borrelia burgdorferi and cytokine induction", Infect Immun, 76, pp.2341~2351 (2008)[DOI]
- Markowicz C, "Inactivation of Lactobacillus rhamnosus GG by fixation modifies its probiotic properties", Can J Microbiol, 62, pp.72~82 (2016)[DOI]
- Barkman C, "Soluble bacterial constituents down-regulate secretion of IL-12 in response to intact Gram-positive bacteria", Microbes Infect, 10, pp.1484~1493 (2008)[DOI]
- Jagger MP, "Inflammatory cytokine(interleukin 6 and tumour necrosis factor alpha)release in a human whole blood system in response to Streptococcus pneumoniae serotype 14 and its capsular polysaccharide", Clin Exp Immunol, 130, pp.467~474 (2002)
- Amar S, "Is Porphyromonas gingivalis cell invasion required for atherogenesis? Pharmacotherapeutic implications", J Immunol, 182, pp.1584~1592 (2009)[DOI]
- Choi EK, "Mechanisms of Porphyromonas gingivalis-induced monocyte chemoattractant protein-1 expression in endothelial cells", FEMS Immunol Med Microbiol, 44, pp.51~58 (2005)[DOI]
- Rengarajan M, "Endothelial cells use a formin-dependent phagocytosis-like process to internalize the bacterium Listeria monocytogenes", PLoS Pathog, 12, pp.e1005603~ (2016)[DOI]