Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures
Thrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Georg Thieme Verlag KG
2022-07-01
|
| Series: | TH Open |
| Subjects: | |
| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/a-1801-2055 |
| _version_ | 1828286391744724992 |
|---|---|
| author | Mallorie Boron Tiffany Hauzer-Martin Joseph Keil Xue-Long Sun |
| author_facet | Mallorie Boron Tiffany Hauzer-Martin Joseph Keil Xue-Long Sun |
| author_sort | Mallorie Boron |
| collection | DOAJ |
| description | Thrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM, is the major circulating TM which is generated by either enzymatic or chemical cleavage of the intact protein under different conditions. Under normal conditions, sTM is present in low concentrations (<10 ng/mL) in the blood but is elevated in several pathological conditions associated with endothelial dysfunction such as cardiovascular, inflammatory, infection, and metabolic diseases. Therefore, sTM level has been examined for monitoring disease development, such as disseminated intravascular coagulation (DIC), sepsis and multiple organ dysfunction syndrome in patients with novel coronavirus disease 2019 (COVID-19) recently. In addition, microvesicles (MVs) that contain membrane TM (MV-TM) have been found to be released from activated cells which also contribute to levels of circulating TM in certain diseases. Several release mechanisms of sTM and MV-TM have been reported, including enzymatic, chemical, and TM mutation mechanisms. Measurements of sTM and MV-TM have been developed and explored as biomarkers in many diseases. In this review, we summarize all these advances in three categories as follows: (1) release mechanisms of circulating TM, (2) methods for measuring circulating TM in biological samples, and (3) correlation of circulating TM with diseases. Altogether, it provides a whole picture of recent advances on circulating TM in health and disease. |
| first_indexed | 2024-04-13T09:31:33Z |
| format | Article |
| id | doaj.art-d6a54f1fb7594c6c8df508ddd863aaad |
| institution | Directory Open Access Journal |
| issn | 2512-9465 |
| language | English |
| last_indexed | 2024-04-13T09:31:33Z |
| publishDate | 2022-07-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | TH Open |
| spelling | doaj.art-d6a54f1fb7594c6c8df508ddd863aaad2022-12-22T02:52:14ZengGeorg Thieme Verlag KGTH Open2512-94652022-07-010603e194e21210.1055/a-1801-2055Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical ProceduresMallorie Boron0Tiffany Hauzer-Martin1Joseph Keil2Xue-Long Sun3Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United StatesDepartment of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United StatesDepartment of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United StatesDepartment of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United StatesThrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM, is the major circulating TM which is generated by either enzymatic or chemical cleavage of the intact protein under different conditions. Under normal conditions, sTM is present in low concentrations (<10 ng/mL) in the blood but is elevated in several pathological conditions associated with endothelial dysfunction such as cardiovascular, inflammatory, infection, and metabolic diseases. Therefore, sTM level has been examined for monitoring disease development, such as disseminated intravascular coagulation (DIC), sepsis and multiple organ dysfunction syndrome in patients with novel coronavirus disease 2019 (COVID-19) recently. In addition, microvesicles (MVs) that contain membrane TM (MV-TM) have been found to be released from activated cells which also contribute to levels of circulating TM in certain diseases. Several release mechanisms of sTM and MV-TM have been reported, including enzymatic, chemical, and TM mutation mechanisms. Measurements of sTM and MV-TM have been developed and explored as biomarkers in many diseases. In this review, we summarize all these advances in three categories as follows: (1) release mechanisms of circulating TM, (2) methods for measuring circulating TM in biological samples, and (3) correlation of circulating TM with diseases. Altogether, it provides a whole picture of recent advances on circulating TM in health and disease.http://www.thieme-connect.de/DOI/DOI?10.1055/a-1801-2055circulating thrombomodulincovid-19endothelial cellmicrovesiclesepsissoluble thrombomodulinthrombomodulinvascular damage |
| spellingShingle | Mallorie Boron Tiffany Hauzer-Martin Joseph Keil Xue-Long Sun Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures TH Open circulating thrombomodulin covid-19 endothelial cell microvesicle sepsis soluble thrombomodulin thrombomodulin vascular damage |
| title | Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures |
| title_full | Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures |
| title_fullStr | Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures |
| title_full_unstemmed | Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures |
| title_short | Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures |
| title_sort | circulating thrombomodulin release mechanisms measurements and levels in diseases and medical procedures |
| topic | circulating thrombomodulin covid-19 endothelial cell microvesicle sepsis soluble thrombomodulin thrombomodulin vascular damage |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/a-1801-2055 |
| work_keys_str_mv | AT mallorieboron circulatingthrombomodulinreleasemechanismsmeasurementsandlevelsindiseasesandmedicalprocedures AT tiffanyhauzermartin circulatingthrombomodulinreleasemechanismsmeasurementsandlevelsindiseasesandmedicalprocedures AT josephkeil circulatingthrombomodulinreleasemechanismsmeasurementsandlevelsindiseasesandmedicalprocedures AT xuelongsun circulatingthrombomodulinreleasemechanismsmeasurementsandlevelsindiseasesandmedicalprocedures |