Thrombomodulin-mediated Cell Adhesion

Huang, Huey-Chun; Shi, Guey‐Yueh; Jiang, Shinn‐Jong; Shi, Chung‐Sheng; Wu, Chujun; Yang, Hsiang-Yu; Wu, Hua‐Lin

doi:10.1074/jbc.m305216200

Cited by 138 publications

(59 citation statements)

References 40 publications

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“…Interestingly, inhibition of TAFI significantly reduced the beneficial effect of recombinant soluble TM on leukocyte infiltration. Other studies showed that the lectin-like domain of TM might be important to maintain the integrity of cell-cell interactions, in order to prevent leukocyte transmigration [211]. However, TM expression and/or function are down-regulated in a variety of clinical conditions associated with inflammation, precisely when it is most necessary [212][213][214].…”

Section: Thrombomodulin and Inflammationmentioning

confidence: 98%

The Multifunctional Protein C System

España¹,

Medina²,

Navarro³

et al. 2005

CMCCHA

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The protein C pathway is a major regulator of blood coagulation, since it controls the conversion of prothrombin to thrombin through a feedback inhibition mechanism. Protein C circulates in plasma as an inactive zymogen and is activated on the surface of endothelial cells by the thrombin-thrombomodulin complex, a process that can be further enhanced when protein C binds to its membrane receptor, the endothelial-cell protein C receptor. Activated protein C (APC) is then released from the complex, binds protein S and inhibits thrombin formation by inactivating coagulation factors Va and VIIIa. The importance of the protein C anticoagulant pathway is emphasized by the increased risk of venous thromboembolism (VTE) associated with protein C and protein S deficiencies, the factor V Leiden mutation, and reduced circulating APC levels. The protein C pathway also plays a significant role in inflammatory processes, since it prevents the lethal effects of E. coli-associated sepsis in animal models and improves the outcome of patients with severe sepsis. APC seems to display anti-apoptotic and neuroprotective activities. Thus, it reduces organ damage in animal models of sepsis, ischemic injury, endothelial cell injury, or stroke. Further research will hopefully widen the current therapeutic perspectives in all these illnesses, where these effects might play a crucial role in their treatment. This review will summarize the mechanisms that contribute to these biological activities of the protein C pathway.

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Section: Thrombomodulin and Inflammationmentioning

confidence: 98%

The Multifunctional Protein C System

España¹,

Medina²,

Navarro³

et al. 2005

CMCCHA

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“…Cellular lysates were prepared as described previously [26,27]. Proteins were resolved using SDS-PAGE and transferred to polyvinylidene difloride (PVDF) membranes.…”

Section: Methodsmentioning

confidence: 99%

Mitomycin C Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes via a Mitochondrial-Mediated Pathway

Yan

Kong

Dong

et al. 2015

Cell Physiol Biochem

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Background/Aims: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. Methods: Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. Results: Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. Conclusion: Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway.

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“…Recent studies suggest that TM plays a role in cell-cell junction, and the lectin-like domain of TM (TMD1) may be important to maintain the integrity of cell-cell interactions. In our study [23], we observed that A2058 melanoma cells transfected with green fluorescent protein (GFP)-tagged TM (TMG) assumed an epithelial-like morphology that clustered closely together with strong cell-cell adhesion, and TM localized predominantly in the intercellular boundaries. However, A2058 cells stably expressing only GFP or lectin domain-deleted TM assumed a fibroblastic-like cell morphology and were dispersed as single cells in nonconfluent cell densities.…”

Section: Tm and Cell Adhesionmentioning

confidence: 96%

The Role of Thrombomodulin in Atherosclerosis: From Bench to Bedside

Shi

2006

CHAMC

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Atherosclerosis remains a leading cause of morbidity and mortality worldwide. In addition to the deposition of cholesterol in the arterial wall, inflammation, cell proliferation and migration play important roles in the pathogenesis of atherosclerosis. Thrombomodulin (TM) is a cell surface-expressed glycoprotein which is predominantly synthesized by vascular endothelial cells and a critical cofactor for thrombin-mediated activation of protein C. Activated protein C is best known for its natural anticoagulant and anti-inflammatory properties. Recent evidence has revealed that TM also has protein C- and thrombin-independent physiological function. This review summarizes recent investigations of TM, giving an overview on the TM unique effects on cellular proliferation, adhesion and inflammation, all of which are important steps in atherosclerosis. The current evidence of TM in the pathogenesis of atherosclerosis will be reviewed, and the associations of TM gene polymorphisms with atherosclerosis are presented. Newly emerging data of the TM in mouse atherosclerosis model demonstrates that TM potentially may have therapeutic role in atherosclerosis.

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Thrombomodulin-mediated Cell Adhesion

Cited by 138 publications

References 40 publications

The Multifunctional Protein C System

The Multifunctional Protein C System

Mitomycin C Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes via a Mitochondrial-Mediated Pathway

The Role of Thrombomodulin in Atherosclerosis: From Bench to Bedside

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