I-191

PAR2-Induced Tissue Factor Synthesis by Primary Cultures of Human Kidney Tubular Epithelial Cells Is Modified by Glucose Availability

Coagulopathies present with patients with diabetes and chronic kidney disease (CKD) aren’t fully understood. Fibrin deposits within the kidney suggest the neighborhood existence of clotting factors including tissue factor (TF). Within this study, we investigated the result of glucose availability around the synthesis of TF by cultured human kidney tubular epithelial cells (HTECs) as a result of activation of protease-activated receptor 2 (PAR2). PAR2 activation by peptide 2f-LIGRLO-NH2 (2F, 2 ┬ÁM) enhanced the synthesis and secretion of active TF (~45 kDa) that was blocked with a PAR2 antagonist (I-191). Treatment with 2F also considerably elevated the intake of glucose in the cell medium and lactate secretion. Culturing HTECs in 25 mM glucose enhanced TF synthesis and secretion over 5 mM glucose, while inclusion of 5 mM 2-deoxyglucose (2DOG) considerably decreased TF synthesis and reduced its molecular weight (~40 kDa). Blocking glycosylation with tunicamycin also reduced 2F-caused TF synthesis while reducing its molecular weight (~36 kDa). To conclude, PAR2-caused TF synthesis in HTECs is enhanced by culture in high concentrations of glucose and covered up by inhibiting either PAR2 activation (I-191), glycolysis (2DOG) or glycosylation (tunicamycin). These results might help let you know that elevated concentrations of glucose promote clotting abnormities in diabetic kidney disease. The use of PAR2 antagonists to deal with CKD ought to be investigated further.

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