Disease relevance of Thbd

• Elevation of Intracellular cAMP Up-Regulated Thrombomodulin mRNA in Cultured Vascular Endothelial Cells Derived from Spontaneous Type-II Diabetes Mellitus Model Rat [1].
• Deficiency of microvascular thrombomodulin and up-regulation of protease-activated receptor-1 in irradiated rat intestine: possible link between endothelial dysfunction and chronic radiation fibrosis [2].
• Intestinal irradiation up-regulates PAR-1 and causes a dose-dependent, sustained deficiency of microvascular TM that is independently associated with the severity of radiation toxicity [2].
• We examined radiation-induced changes in endothelial thrombomodulin (TM) and protease-activated receptor-1 (PAR-1) in irradiated intestine, and their relationship to structural, cellular, and molecular aspects of radiation injury [2].
• The increased levels of serum fibrin degradation products (FDP), fibrin deposition within liver sinusoids, injury of SECs and liver dysfunction induced by LPS in our rat model was improved by recombinant TM treatment [3].

High impact information on Thbd

• Interventions aimed at preserving or restoring endothelial TM or blocking PAR-1 should be explored as strategies to increase the therapeutic ratio in clinical radiation therapy [2].
• The number of TM-positive vessels correlated with all parameters of radiation enteropathy and, after adjusting for radiation dose and observation time in a statistical model, remained independently associated with neutrophil infiltration, intestinal wall thickening, and collagen I accumulation [2].
• In the first week of the disease period, immunohistochemical labeling of tubular VEGF intensified, with accompanying deformation and dilation of adjacent thrombomodulin (TM)-positive PTC lumina; an angiogenic response of endothelial cells was demonstrated with Ki67 and TM double-staining [4].
• Thrombomodulin staining revealed that within 3 to 8 wk, there was a significant (P < 0.001) decline in the number of PTC, accompanied by a marked accumulation of macrophages, T cells, and fibrotic material [5].
• Only limited effects of aminoguanidine treatment on peripheral nerve function, (Na+,K+)-ATPase activity and thrombomodulin expression in streptozotocin-induced diabetic rats [6].

Chemical compound and disease context of Thbd

• Bacterial lipopolysaccharide decreases thrombomodulin expression in the sinusoidal endothelial cells of rats -- a possible mechanism of intrasinusoidal microthrombus formation and liver dysfunction [3].
• Pioglitazone feeding also upregulated the aortic expression of cNOS and thrombomodulin; both are considered important factors in platelet aggregation and thrombus formation in vivo [7].

Biological context of Thbd

• Rapid atrial pacing for 8 hours significantly decreased TM and TFPI mRNA levels in the left atrium but not in the ventricle, leading to the downregulation of their immunoreactive proteins [8].
• CONCLUSIONS: Rapid atrial pacing acutely downregulated the gene expression of TM and TFPI in the atrial endocardium, thereby inducing local coagulation imbalance on the internal surface of the atrial cavity [8].
• Rat primary MCs were stably transfected (using strontium phosphate DNA coprecipitation) with a plasmid containing the gene for rat thrombomodulin (TM), a transmembrane glycoprotein that functions as an essential cofactor for the physiological activation of the anticoagulant protein C by the enzyme thrombin [9].
• This action of thrombomodulin may serve to protect vasculature from thrombin-induced vasoconstriction during conditions of endothelial injury known to increase plasma and cellular levels of thrombomodulin [10].
• RESULTS: The trial of gene transfection using variable doses of DNAs confirmed that 7.5 microg of total DNAs was the most efficient quantity for thrombomodulin gene transfection to IVCs, although accompanying an increase of gene expression in other downstream organs [11].

Anatomical context of Thbd

• TM was localized on the plasma membrane of the pericryptal fibroblasts which existed in the pericryptal spaces between the basal lamina of the epithelium and the collagenous sheets around the base of the crypt [12].
• The functional significance of TM in pericryptal fibroblasts is discussed [12].
• In contrast to pericryptal fibroblasts, TM was not localized in subepithelial fibroblasts in the villi or smooth muscle cells in the lamina muscularis mucosae and the muscularis [12].
• This report describes the distribution and localization of TM in the rat duodenum by light and electron microscopic immunohistochemistry [12].
• Thrombomodulin and tissue factor pathway inhibitor in endocardium of rapidly paced rat atria [8].

Associations of Thbd with chemical compounds

• Therefore, elevation of intracellular cAMP by db-cAMP or cilostazol up-regulated TM mRNA expression in cultured VECs from OLETF rats [1].
• The results so far obtained indicate that some specific endothelial membrane proteins (e.g., thrombomodulin, functional thrombin receptor) are distributed about evenly between the B and NB subfractions, whereas others are restricted to the NB subfraction (e.g., angiotensin converting enzyme, podocalyxin) [13].
• Thrombomodulin concentrations were increased (p < 0.01) in diabetic rats compared with those in non-diabetic controls and unaffected by aminoguanidine treatment [6].
• ADP and arachidonic acid-induced platelet aggregation and the expression of constitutive nitric oxide synthase (cNOS) and thrombomodulin in aorta were measured [7].
• 1Alpha,25-dihydroxyvitamin D3 (active form of vitamin D3; vitamin D3) has been reported to induce the upregulation of thrombomodulin and downregulation of tissue factor (TF) on monocytes [14].

Regulatory relationships of Thbd

• Thrombomodulin (TM) contributes to the inactivation of thrombin which activates protein C, a major anticoagulant and anti-inflammatory protein [12].

Other interactions of Thbd

• As judged by a thrombin-dependent protein C activation assay, such MC membrane-bound TM was biologically active [9].
• The purpose of this study was to determine whether thrombomodulin would alter thrombin-induced vasoconstriction, thought to be mediated predominantly by PAR-1, but not PAR-2, which mediates vascular relaxation [10].
• CONCLUSIONS: Transferrin receptor-facilitated in vivo gene transfer to the inferior vena cava resulted in sufficient thrombomodulin gene expression immediately after graft implantation and subsequent maintenance of thromboresistance even after exposure to arterial pressure [11].

Analytical, diagnostic and therapeutic context of Thbd

• TM mRNA expression in cultured VECs from OLETF rats was increased 2.1-fold at 24 h after treatment with db-cAMP (3 mmol/L) [1].
• PAR-1 protein was localized immunohistochemically, and cells expressing TM or PAR-1 transcript were identified by in situ hybridization [2].
• Modification of thrombomodulin expression was studied by Western blotting and quantitative reverse transcription-PCR [15].
• We measured TM in cultured SECs by enzyme immunoassay, functional analysis and real-time polymerase chain reaction (PCR) [3].
• We failed to demonstrate suppressed TM expression in the kidneys of septic animals using immunofluorescence [16].

References