Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of nephrosis in rats with aminonucleoside of puromycin (ANP) was followed by an increase in urinary protease activity, measured by the cleavage of 14C-globin, as well as in antiprotease activity measured by trypsin inhibition. The excretion of protease and protease inhibitor coincided with but did precede the onset of proteinuria when the ANP was injected subcutaneously for 5 days and lagged after proteinuria when the ANP was given as a single intravenous dose. Serum protease activity did not change throughout ANP treatment or later, whereas serum antiprotease capacity declined coincidently with proteinuria, most probably due to the loss in urine. Kidney proteolytic activity was markedly reduced in ANP nephrosis. Treatment of rats with proteolysis inhibitors, trasylol, episilon-aminocaproic acid, soybean trypsin inhibitor, or hexapron, together with ANP failed to prevent, delay or reduce the proteinuria. We believe that the urinary protease in ANP nephrosis does not originate from the circulation but from the release of kidney protease as a consequence of the glomerular lesion, and does not appear to be involved in its causation.
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PMID:Urine protease and antiprotease activity in experimental aminonucleoside nephrotoxicity. 703 8

Anti-rat glomerular basement membrane (GBM) rabbit serum was produced by immunizing rabbits with the supernatant substance of trypsin-digested rat GBM. Nephritis was induced in rats by a single intravenous administration of 0.25 ml of anti-serum and changes in pathohistological and biochemical parameters during the process of the disease were investigated in comparison with those of Masugi nephritis and the modified type of Masugi nephritis previously reported. In light microscopic studies, histological changes seen in the kidneys closely resembled those of typical human glomerulonephritis. Changes such as hypercellularity, adhesion between capillary wall and Bowman's capsule, crescent formation and hyalinization in glomeruli and interstitial infiltration were the most pronounced on the 30th day after the anti-serum injection. In immunofluorescent studies, a linear fixation of rabbit IgG was observed along the GBM from the 1st day and the staining of a certain intensity was preserved throughout the experimental periods. A linear staining with anti-rat IgG serum was recognized from the 10th day. The fixation of fibrinogen was also seen in not only the glomerular capillary walls, but also in Bowman's space after the 10th day. Proteinuria significantly increased from the 1st day, reached a peak of 12 times the control level, and thereafter gradually decreased. The patterns of progress of urinary alkaline phosphatase and N-acetyl-beta-glucosaminidase activities were much the same as those seen in cases of proteinuria and the levels at their peak times were about 10 and 3 times control levels, respectively. Plasma urea nitrogen level transiently increased on the 5th day and then reverted to the control level by the 30th day. Plasma cholesterol levels were significantly high from the 5th to the 20th days. It is concluded that glomerular damages in this model are more severe, so-called, "nephritic type" and continue for longer periods than in cases of Masugi nephritis, however, do not differ in degree and duration from findings in the modified type of Masugi nephritis.
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PMID:[Pharmacological studies on experimental nephritic rats (11). Changes in pathohistological and biochemical parameters in anti-rat GBM rabbit serum-induced nephritis (author's transl)]. 728 45

Heymann nephritis developed in rats immunized with brush border membrane fractions isolated from rat kidney tubules. Glomerular autoantibodies eluted from cryostat sections of nephritic kidneys reacted in immunoelectron microscopy with the outer surface of isolated brush border membrane vesicles. This indicates that the autoantigens are plasma membrane components. To characterize further the chemical nature of the nephritogenic autoantigens, we treated the brush border membranes with trypsin and sodium deoxycholate, and the solubilized membranes were then fractionated by lectin affinity chromatography. The polypeptide composition of the fractions was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The capacity of the membrane fractions to induce Heymann nephritis was assessed by observing the development of typical renal lesions, antibrush border autoantibodies, and proteinuria in rats immunized with these fractions. The results suggest that the nephritogenic autoantigen is an integral component of the brush border membrane of kidney proximal tubules and has an affinity for Lens culinaris agglutinin. This indicates that it is a glycoprotein and has mannosyl and/or glycosyl groups exposed in its oligosaccharide side chains.
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PMID:Heymann nephritis induced by kidney brush border glycoproteins. 744 31

This study investigated whether protease treatment ameliorates the progressive course of chronic failure in the rat model of subtotal nephrectomy. Fourteen male Wistar rats underwent 5/6 nephrectomy, and were randomized into a control group (C, n = 7) given 2 ml of 0.9% NaCl intraperitoneally (i.p.) daily, and a study group (P, n = 7) treated with 12 mg Phlogenzym (combination of trypsin, bromelain, and rutosid) in 2 ml saline i.p. daily. After 6 weeks treatment, the Phlogenzym group showed lower proteinuria (C: 19.6 +/- 9.1 vs. 10.2 +/- 6.2 mg/24 h, p < 0.05). Endogenous creatinine clearance was higher (C: 192.3 +/- 99.4, P: 300.5 +/- 47.9 microliters/min per 100 g, p < 0.05), while plasma creatinine was decreased (C: 106.7 +/- 33.9, P: 76.0 +/- 6.3 mumol/l, p < 0.01). Blood urea nitrogen levels did not change, although urea clearance tended to a higher level in the protease-treated rats. Decreased renal formation of cytokines was reflected by a lower urinary excretion ratio of transforming growth factor (TGF)-beta/ creatinine (C: 0.363 +/- 0.183, P: 0.232 +/- 0.085 ng TGF-beta/mg creatinine, p < 0.05). Renal morphology revealed less infiltration of mononuclear cells and an amelioration of interstitial fibrosis as expressed by the volume index of the cortical region (C: 17.17 +/- 1.43; P: 12.3 +/- 0.5%, p < 0.001). In addition, the activities of lysosomal proteinases (cathepsin B, L + B, and H), which are decreased in the remnant kidney model of chronic renal failure, were significantly higher in the enzyme-treated group both in isolated glomeruli and proximal tubules. The body and kidney weight tended to be lower, probably due to a catabolic action of the enzymes. In summary, we provide evidence that protease treatment may be beneficial in a nonimmune mediated renal disease. Phlogenzym ameliorated the course of chronic renal failure in the rat model of subtotal nephrectomy and retarded the development of tubulointerstitial fibrosis. Decreased cytokine formation in the remnant kidney is supposed to play a key role.
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PMID:Effects of protease therapy in the remnant kidney model of progressive renal failure. 938 36

This study investigated the possible beneficial effect of intraperitoneal proteolytic enzyme administration on the development of hypertension-induced renal injury in the rat model of 2-kidney 1-clip (2K1C) Goldblatt hypertension. Male Wistar rats (120-150 g) underwent either sham surgery (control, n = 5) or clipping of the left renal artery. From day one 2K1C rats were randomized into 2 groups, placebo treatment (n = 7), and proteolytic enzyme treatment (n = 9). To the verum group a fixed mixture of trypsin (2.42 mg), bromelain (4.54 mg), and rutin (5.04 mg) dissolved in 2 ml of sterile 0.9% NaCl was administered intraperitoneally daily, while the placebo group received only vehicle. Rats were pair-fed. The duration of the study was 7 weeks. All 2K1C rats developed hypertension and the mean values of systolic blood pressure (SBP) did not differ significantly between the groups at any time recorded (SBP at sacrifice: controls 122.0 +/- 8.5 mm Hg; placebo 191.4 +/- 7. 6 mm Hg; enzyme 180.5 +/- 6.5 mm Hg). Enzyme treatment prevented the rise in proteinuria (controls 12.4 +/- 2.6 mg/24 h; placebo 19.7 +/- 3.9 mg/24 h; enzyme 12.2 +/- 1.3 mg/24 h; p < 0.05) and ameliorated the increase in serum urea concentrations. Histomorphologically, signs of malignant nephrosclerosis were not found in control rats, while they were present in 4/7 (57%) of placebo-treated rats, but only in 1/9 (11%) of the enzyme-treated group. The volume fraction of renocortical interstitium was increased in both 2K1C groups in comparison with controls; however, enzyme treatment decreased the accumulation of interstitial tissue significantly (-22%) compared to placebo treatment. Cellular infiltration with mononuclear cells was also lower in the protease-treated group. To summarize, in the rat model of 2K1C hypertension, systemic treatment with proteases ameliorates the severity of nephrosclerosis and tubulointerstitial fibrosis in the non-clipped kidney, as well as proteinuria, without affecting high blood pressure.
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PMID:Effect of chronic therapy with proteolytic enzymes on hypertension-induced renal injury in the rat model of Goldblatt hypertension. 984 40

It was found in our previous paper that edema, proteinuria, hypertension (EPH)-gestosis-associated accumulation of collagen in the umbilical cord artery (UCA) is a result of increased biosynthesis and decreased degradation of this protein. It is known that the activity of collagenolytic enzymes is a main factor regulating collagen degradation rate in various tissues. For this reason it was decided to evaluate the effect of EPH-gestosis on the activity of proteolytic enzymes which may be involved in collagen degradation in the UCA wall. Proteolytic activity against bovine serum albumin, reconstituted collagen fibres and gelatin were evaluated. Latent forms of proteolytic enzymes were activated by the action of trypsin, p-chloromercuric benzoate (PCMB) and p-aminophenylmercuric acetate (APMA). A low activity of gelatinase (type IV collagenase) was detected in the extracts from the wall of the umbilical cord artery. This enzyme increased its activity several times after the action of trypsin, PCMB and APMA. EPH-gestosis results in a distinct reduction in gelatinase activity. Despite the action of activating agents the gelatinase from EPH-gestosis UCAs was considerably lower in comparison to control UCAs. It can be concluded that gelatinase of the umbilical cord artery forms an inactive complex with a tissue inhibitor of metalloproteinases. Such a complex dissociates under the action of trypsin, PCMB or APMA or sodium dodecyl sulphate. The decrease of gelatinolytic activity in the umbilical cord artery may be a factor that reduces the breakdown of collagen in the arterial wall and promotes an accumulation of this protein. The accumulation of collagen with simultaneous reduction in elastin content in the UCA may be the factors which reduce the elasticity of arterial wall and decrease the blood flow in the fetus of woman with EPH-gestosis.
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PMID:EPH-gestosis (pre-eclampsia)-induced decrease of gelatinase activity may promote an accumulation of collagen in the umbilical cord artery. 1069 Jun 79

Recent evidence suggests a role for mast cells in the pathogenesis of renal scarring in various glomerulopathies, therefore the present study was undertaken to evaluate whether mast cells have a role in tubulointerstitial fibrosis in rebiopsied patients with idiopathic mesangial proliferative glomerulonephritis (MPG) and to examine a possible relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. Seventeen patients with idiopathic mesangial proliferative glomerulonephritis, in whom renal biopsies were repeated and for whom light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available were examined quantitatively. Morphometric investigations were performed by means of a computer image analysis system. The study revealed that at the rebiopsy proteinuria was significantly lower as compared with the first biopsy. On the other hand, the mean values of the interstitial tryptase positive cells, expression of alpha-SMA, interstitial volume and CD68+ cells were at rebiopsy significantly increased. The mean values of CD45RB+, CD43+ and CD20+ cells did not differ significantly in these groups. In both initial biopsy and rebiopsy groups there were significant positive correlations between interstitial tryptase positive cells and interstitial expression of alpha-SMA, interstitial volume, and CD68+ cells. The present quantitative study may suggest that despite of the clinical improvement at rebiopsy, MPG is a progressive glomerular disease, and point to a role of mast cells in this process.
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PMID:Immunohistochemical analysis of the interstitial mast cells in rebiopsied patients with idiopathic mesangial proliferative glomerulonephritis. 1609 67

Increased infiltration of the kidney by mast cells is associated with proteinuria, and interstitial fibrosis in various renal diseases. Mast cells produce serine proteases including tryptase and chymase (MCC) that act via protease-activated receptors (PARs) to induce synthesis of fibrogenic cytokines by renal cells. In the present study, we investigated direct effect of MCC and role of PARs on glomerular albumin permeability (P(alb)). Isolated rat glomeruli were incubated with MCC (0.1, 1, 10, and 100 ng/ml) for 5-30 min in presence or absence of PAR-1 and PAR-2 blocking antibodies. P(alb) was determined from the change in glomerular volume in response to an albumin oncotic gradient. The effect of direct activation of PARs on P(alb) was verified by incubating glomeruli with synthetic hexapeptide known to activate PAR-1 and PAR-2. MCC increased P(alb) of isolated rat glomeruli in a dose- and time-dependent manner. Blocking PAR-2 prevented MCC-mediated increase in P(alb). RT-PCR analysis of glomerular RNA demonstrated the presence of constitutively expressed PAR-1, -2, and -3 and low levels of PAR-4. In addition, direct activation of PAR-2 by hexapeptide SLIGKV increased P(alb) comparable to MCC, whereas PAR-1 activation by TFLLRN had no effect on P(alb). Our results document that MCC induces increase in P(alb) and that this effect is mediated through PAR-2. MCC may also play a role in renal scarring. We propose that inhibiting MCC activity or blocking the activation of PAR-2 may provide new targets for therapy in renal diseases.
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PMID:Chymase increases glomerular albumin permeability via protease-activated receptor-2. 1710 4

Protease-activated receptor-2 (PAR-2) is a cellular receptor expressed prominently on epithelial, mesangial, and endothelial cells in the kidney and on macrophages. PAR-2 is activated by serine proteases such as trypsin, tryptase, and coagulation factors VIIa and Xa. It induces pleiotropic effects including vasodilatation, increasing plasminogen activator inhibitor (PAI-1) expression, mesangial cell proliferation, and cytokine production by macrophages. The role of PAR-2 in renal inflammation was studied in antiglomerular basement membrane antibody-induced crescentic glomerulonephritis (CGN) using PAR-2-deficient (PAR-2(-/-)) mice and wild-type littermate controls. PAR-2(-/-) mice had reduced crescent formation, proteinuria, and serum creatinine compared with wild-type mice 21 days after initiation of CGN. Glomerular accumulation of CD4(+) T cells and macrophages and the number of proliferating cells in glomeruli were similar in both groups. Glomerular fibrin deposition was significantly reduced in PAR-2(-/-) mice, and this was associated with reduced renal plasminogen activator inhibitor expression and increased renal matrix-metalloprotinase-9 activity. These results demonstrate a proinflammatory role for PAR-2 in CGN that is independent of effects on glomerular leukocyte recruitment and mesangial cell proliferation. PAR-2-mediated augmentation of renal plasminogen activator inhibitor expression and inhibition of matrix-metalloprotinase-9 activity may contribute to increased glomerular fibrin accumulation and glomerular injury in CGN.
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PMID:Protease-activated receptor-2 augments experimental crescentic glomerulonephritis. 1764 Sep 68

This study was aimed at the search of urinary biomarkers which might help to predict the clinical response of IgA nephropathy (IgAN) patients to angiotensin converting enzyme inhibitors (ACEi). First, we studied the urinary proteome of 18 IgAN patients (toward 20 healthy controls) who had been chronically treated with ACEi by using 2-D PAGE coupled to nano-HPLC-ESI-MS/MS analysis. We identified 3 proteins, kininogen (p = 0.02), inter-alpha-trypsin-inhibitor heavy chain 4 (35 kDa fragment) (p = 0.02) and transthyretin (p<0.0001), whose urinary excretion was different in IgAN patients' responders when compared to those who had not responded to ACEi. A reduction of daily proteinuria >50% and a stable renal function over time were used to classify patients as responders. Then, we adopted immunoblotting to confirm the predictive power of one of the above proteins, kininogen, in 20 patients with biopsy-proven IgAN, before starting any therapy. Thus, we confirmed that very low levels of kininogen urine excretion were indeed predictive of an inadequate or absent clinical response to ACEi therapy of IgAN patients, after 6-month follow-up. Concluding, the analysis of urine proteome of IgAN patients generated a set of proteins which distinguished subjects responsive to ACEi from those unresponsive to the inhibition of renin-angiotensin system (RAS).
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PMID:Urine protein profile of IgA nephropathy patients may predict the response to ACE-inhibitor therapy. 1809 57


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