RGD Reference Report - The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritis. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritis.

Authors: Van de Wouwer, M  Plaisance, S  De Vriese, A  Waelkens, E  Collen, D  Persson, J  Daha, MR  Conway, EM 
Citation: Van de Wouwer M, etal., J Thromb Haemost. 2006 Aug;4(8):1813-24.
RGD ID: 5685015
Pubmed: PMID:16879225   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1538-7836.2006.02033.x   (Journal Full-text)

BACKGROUND: Thrombomodulin (TM) is predominantly a vascular endothelial cell plasma membrane glycoprotein that, via distinct structural domains, interacts with multiple ligands, thereby modulating coagulation, fibrinolysis, complement activation, inflammation and cell proliferation. We previously reported that by mediating signals that interfere with mitogen-activated protein kinase and nuclear factor kappaB pathways, the amino-terminal C-type lectin-like domain of TM has direct anti-inflammatory properties. METHODS: In the current study, we use murine models of acute inflammatory arthritis and biochemical approaches to assess the mechanism by which the lectin-like domain of TM modifies disease progression. RESULTS: Mice lacking the lectin-like domain of TM (TM(LeD/LeD)mice) develop inflammatory arthritis that is more rapid in onset and more severe than that developed in their wildtype counterparts. In two models of arthritis, treatment of mice with recombinant soluble lectin-like domain of TM significantly suppresses clinical evidence of disease and diminishes monocyte/macrophage infiltration into the synovium, with weaker expression of the pro-inflammatory high mobility group box chromosomal protein 1. While thrombin-TM mediated activation of thrombin activatable fibrinolysis inhibitor inactivates complement factors C3a and C5a, we show that TM has a second independent mechanism to regulate complement: the lectin-like domain of TM directly interferes with complement activation via the classical and lectin pathways. CONCLUSIONS: These data extend previous insights into the mechanisms by which TM modulates innate immunity, and highlight its potential as a therapeutic target for inflammatory diseases.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
THBDHumanExperimental Arthritis  ISOThbd (Mus musculus) RGD 
ThbdRatExperimental Arthritis  ISOThbd (Mus musculus) RGD 
ThbdMouseExperimental Arthritis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Thbd  (thrombomodulin)

Genes (Mus musculus)
Thbd  (thrombomodulin)

Genes (Homo sapiens)
THBD  (thrombomodulin)


Additional Information