Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.
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PMID:A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells. 792 84

The association between plasma coagulant activity and the presence of diabetic nephropathy was investigated in 31 patients with Type 1 diabetes, 12 with and 19 without nephropathy, and in 11 healthy subjects. Thrombin generation was assessed by computer assisted chromogenic method and expressed as time (in seconds) to 50% maximal thrombin activity (T50). Factor VIII:C levels related to thrombin activity, glycaemic control, and renal function. Median (IQ) FVIII:C concentration was increased in patients with nephropathy (1590 (1130-1900) IU l-1) compared to those without renal disease and with controls (960 (750-1090); 1020 (810-1100) IU l-1, p < 0.01, respectively). There were no significant differences in T50 values between the groups. FVIII:C correlated with age in all subjects and in the diabetic group (r = 0.33, p = 0.036; r = 0.39, p = 0.031) and inversely with T50 in all subjects and in controls (r = -0.35, p = 0.02; r = -0.62, p = 0.04). In all subjects and in patients, FVIII:C was related to urinary albumin excretion and creatinine clearance. FVIII:C and T50 were not related to HbA1c. The results show that FVIII:C levels are increased in Type 1 diabetes complicated by nephropathy and are related to degree of renal impairment but not levels of glycaemia. No associated enhancement of plasma procoagulant activity was detected.
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PMID:Thrombin generation and factor VIII:C levels in patients with type 1 diabetes complicated by nephropathy. 850 16

Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis. The progression of renal lesions to fibrosis involves several mechanisms, among which the inhibition of extracellular matrix (ECM) degradation appears to play an important role. Two interrelated proteolytic systems are involved in matrix degradation: the plasminogen activation system and the matrix metalloproteinase system. The plasminogen activator inhibitor type 1 (PAI-1), as the main inhibitor of plasminogen activation, regulates fibrinolysis and the plasmin-mediated matrix metalloproteinase activation. PAI-1 is also a component of the ECM, where it binds to vitronectin. PAI-1 is not expressed in the normal human kidney but is strongly induced in various forms of kidney diseases, leading to renal fibrosis and terminal renal failure. Thrombin, angiotensin II, and transforming growth factor-beta are potent in vitro and in vivo agonists in increasing PAI-1 synthesis. Several experimental and clinical studies support a role for PAI-1 in the renal fibrogenic process occurring in chronic glomerulonephritis, diabetic nephropathy, focal segmental glomerulosclerosis, and other fibrotic renal diseases. Experimental models of renal diseases in PAI-1-deficient animals are in progress, and preliminary results indicate a role for PAI-1 in renal fibrogenesis. Inhibition of PAI-1 activity or of PAI-1 synthesis by specific antibodies, peptidic antagonists, antisense oligonucleotides, or decoy oligonucleotides has been obtained in vitro, but needs to be evaluated in vivo for the prevention or the treatment of renal fibrosis.
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PMID:Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis. 1104 3

Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Disturbances in hemostasis may play a role in the vascular complications of diabetes mellitus. It has been postulated that TAFI-Thrombin Activatable Fibrinolysis Inhibitor, newly described glycoprotein, couples two opposite systems: coagulation and fibrinolysis. The aim of the work was to study TAFI concentration in hemodialyzed and peritoneally dialyzed diabetic and non-diabetic patients. We assessed: TAFI concentration, markers of ongoing coagulation: thrombin-antithrombin complexes, prothrombin fragments 1 + 2 (markers of TAFI activation), a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes, a marker of TAFI cataliser to TAFIa-thrombomodulin using commercially available kits. All four groups studied did not differ in regard to fibrinogen, thrombomodulin, plasmin-antiplasmin complexes, and TAFI concentration. Both groups of dialyzed diabetic patients have higher concentration of markers of ongoing coagulation when compared to dialyzed non-diabetic patients. Hypercoagulable state observed in dialyzed diabetic patients may contribute to the higher cardiovascular mortality in these population.
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PMID:[Thrombin activatable fibrinolysis o inhibitor-TAFI- in dialyzed patients with diabetic nephropathy]. 1468 22