The Role of the Plasminogen/Plasmin System in Inflammation of the Oral Cavity

Tetiana Yatsenko; Maksym Skrypnyk; Olga Troyanovska; Morikuni Tobita; Taro Osada; Satoshi Takahashi; Koichi Hattori; Beate Heissig

doi:10.3390/cells12030445

The Role of the Plasminogen/Plasmin System in Inflammation of the Oral Cavity

Cells. 2023 Jan 30;12(3):445. doi: 10.3390/cells12030445.

Authors

Tetiana Yatsenko¹, Maksym Skrypnyk¹, Olga Troyanovska¹, Morikuni Tobita², Taro Osada³, Satoshi Takahashi⁴, Koichi Hattori⁵, Beate Heissig¹

Affiliations

¹ Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
² Department of Oral and Maxillofacial Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
³ Department of Gastroenterology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu-Shi 279-0021, Japan.
⁴ Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
⁵ Center for Genome and Regenerative Medicine, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.

Abstract

The oral cavity is a unique environment that consists of teeth surrounded by periodontal tissues, oral mucosae with minor salivary glands, and terminal parts of major salivary glands that open into the oral cavity. The cavity is constantly exposed to viral and microbial pathogens. Recent studies indicate that components of the plasminogen (Plg)/plasmin (Pm) system are expressed in tissues of the oral cavity, such as the salivary gland, and contribute to microbial infection and inflammation, such as periodontitis. The Plg/Pm system fulfills two major functions: (a) the destruction of fibrin deposits in the bloodstream or damaged tissues, a process called fibrinolysis, and (b) non-fibrinolytic actions that include the proteolytic modulation of proteins. One can observe both functions during inflammation. The virus that causes the coronavirus disease 2019 (COVID-19) exploits the fibrinolytic and non-fibrinolytic functions of the Plg/Pm system in the oral cavity. During COVID-19, well-established coagulopathy with the development of microthrombi requires constant activation of the fibrinolytic function. Furthermore, viral entry is modulated by receptors such as TMPRSS2, which is necessary in the oral cavity, leading to a derailed immune response that peaks in cytokine storm syndrome. This paper outlines the significance of the Plg/Pm system for infectious and inflammatory diseases that start in the oral cavity.

Keywords: COVID-19; SARS-CoV-2; cytokine; fibrinogen; fibrinolysis; inflammation; oral cavity; plasmin; salivary gland; suPAR; tPA.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Fibrinolysin / metabolism
Humans
Inflammation
Mouth
Plasminogen* / metabolism
Tissue Plasminogen Activator / metabolism

Substances

Fibrinolysin
Plasminogen
Tissue Plasminogen Activator

Grants and funding

This work was supported partly by grants from the Japan Society for the Promotion of Science, Kiban C grant no. 21K08404 (K.H.), 21K08692 (T.O.), 22K070206 (S.T.), Grant-in-Aid for JSPS Fellows 22F21773 (B.H.); the Japanese Society of Hematology Research Grant (K.H.), grants from Nakatani Foundation (K.H.), Terumo Life Science Foundation (K.H.), Okinaka Memorial Institute for Medical Research (K.H.), and a grant from the Institute of Medical Science the University of Tokyo Joint Research (K.H., B.H.).