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)

Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.
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PMID:Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats. 790 49

1. Fibronectin does not correlate with the grade of proteinuria. 2. Fibronectin does not correlate with birth weight. 3. Fibronectin level is not elevated in pregnancy-induced hypertension and preeclampsia. 4. Fibronectin level is elevated in cases of preeclampsia, combined with chronic placental insufficiency respectively intrauterine growth retardation. 5. There is a statistic significant difference between pregnancy-induced hypertension/preeclampsia with or with out placental insufficiency. 6. Extremely problematic pregnancies ended in all pregnancies with values of fibronectin above 0.4 g/l in caesarean section without knowledge of the elevated fibronectin level at the time of operation. 7. In the group of pregnancy-induced hypertension the fibronectin level is elevated in relation to control group. This increase is particularly evident, if a placental insufficiency is concontinant with preeclampsia.
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PMID:[Critical evaluation of fibronectin in pregnancy-induced hypertension/pre-eclampsia and placental insufficiency]. 804 91

Gestational proteinuric hypertension (GPH), a major cause of maternal death, may be characterised by hypertension and proteinuria alone or may progress to disturbed coagulation and multiorgan failure. Since the condition can only be reversed by termination of pregnancy, there is a need for reliable indicators of severity. We found circulating levels of tissue plasminogen activator (tPA) (27.98 +/- 2.12 v. 7.17 +/- 0.81 ng/ml, mean +/- SEM), fibrin(ogen) degradation products (FDP) (7.55 +/- 1.99 v. 1.92 +/- 0.47 micrograms/ml) and fibronectin (221 +/- 15.2 v. 120 +/- 15.2 micrograms/ml) to be significantly increased in 21 patients with severe GPH when compared with 21 normotensive, age- and gestational age-matched pregnant controls. More importantly, patients who developed severe GPH showed a progressive increase in tPA and FDP levels with time. This was in contrast to patients who had hypertension and proteinuria alone, in whom tPA and FDP concentrations did not increase. Parallel measurements did not reveal a fall in platelet count or an increase in urinary protein excretion in patients who subsequently progressed to severe disease. Our findings may be of assistance to clinicians faced with the need to prolong pregnancy in patients with GPH in order to ensure fetal viability.
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PMID:Serial measurements of circulating tissue plasminogen activator and fibrin(ogen) degradation products predict outcome in gestational proteinuric hypertension. 811 15

Diabetic nephropathy is characterized by albuminuria which proceeds to overt proteinuria. The highly negatively stained HS side chain of heparan sulphate proteoglycan (HSPG) is a major determinant of the charge-dependent permeability of the GBM. We set out to study the presence of HS and HSPG in the GBM of patients with diabetic nephropathy using newly developed monoclonal antibodies, and to compare HSPG expression to the expression of other previously investigated glomerular extracellular matrix compounds. Immunohistochemically, glomerular extracellular matrix components were analysed in 14 renal biopsies of patients with diabetic nephropathy and compared with those of normal control subjects. Monoclonal antibodies used were: JM403 against the HS side chain of GBM HSPG and JM72 against the HSPG-core protein. Also, a polyclonal antiserum (B31) against human GBM-HSPG-core protein was used. Additionally, antibodies were used against collagen types I, III, IV and against alpha 1 (IV)NC, alpha 3(IV)NC and fibronectin. Staining was scored for intensity and for staining pattern by four independent observers who had no previous knowledge of the sample origin. No glomerular staining was seen for collagen type I. Collagen type III was present in some diabetic nodules. Anti-collagen type IV showed a decreased GBM staining in patients with diabetic nephropathy (p = 0.04). With anti-alpha 1 (IV)NC no changes in GBM staining intensity were observed; with anti-alpha 3 (IV)NC brilliant GBM staining was seen in both groups. Increased mesangial staining (p = 0.003) was seen with anti-collagen type IV in biopsies with nodular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of glomerular extracellular matrix components in human diabetic nephropathy: decrease of heparan sulphate in the glomerular basement membrane. 748 52

Morphological examination of renal biopsies from 90 women with preeclampsia (PE), assessment of the clinical data and clinicomorphological correlations produced the following results: 1. By light-microscopy the renal lesions in PE imitate a picture of glomerulonephritis of mesangial type with different degrees of severity. 2. Morphometric investigations confirmed the impression gained by light-microscopy of swelling of endothelial cells and podocytes as well as endocapillary cell proliferation and enlargement of the glomeruli. 3. The immunohistological findings are non-specific and argue against immune complex deposition, but are suggestive of insudative processes. In addition immunohistological investigations of fibronectin and factor VIII-associated antigen reveal a pathogenetic relevant alteration of endothelial cell. 4. Electronmicroscopy is the most valid diagnostic method allowing subdivision of the quantitative different lesions in various degrees of severity. Furthermore the use of this method allows elucidation of the dynamics of the underlying disease process, which progresses through successive stages i.e. early, fully developed and late stage, supporting the reversibility of these glomerular lesions. 5. Close correlations are found between the clinical parameters and morphological findings in nephropathy in pregnancy-induced hypertension. The hypertension, proteinuria and nephrotic syndrome, which characterize the clinical picture, correlate with the severity of the glomerular lesions and the further course of the disease. Moreover, hypertension also correlates with mesangial and subendothelial deposits and with focal segmental hyalinosis and sclerosis, occurring in some cases. The focal segmental hyalinosis and sclerosis should be regarded as hyperperfusion-lesions indicating benign nephrosclerosis and developing only facultatively in PE. 6. The first morphological substrate of nephropathy in pregnancy-induced hypertension with the key to pathogenesis present itself as endothelial lesion, possibly caused by oxygen free radicals, lipid-peroxides or hyperfusion. In result of the endothelial lesion an imbalance of the different mediator systems i.e. thromboxane-prostacyclin, endothelin-EDRF with dominance of vasoconstrictive reactions would be effective. Thus the following induction of coagulative, vasoconstrictive and proliferative processes results in the characteristic glomerular lesions in PE.
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PMID:[Nephropathy in pregnancy--an endothelial lesion?]. 817 90

Clusterin is a normal plasma protein, shown to be an inhibitor of reactive complement hemolysis and a component of the fluid phase SC5b-9 terminal complement complexes. It is a component of glomerular immune deposits in human and experimental glomerulonephritis. Using the complement-dependent isolated perfused rat kidney model of autologous phase passive Heymann nephritis, we have studied the effect of clusterin depletion of perfused plasma on the development of glomerular injury. Kidneys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to < or = 30%, or control plasma depleted of plasma fibronectin. Glomerular injury was then initiated by the addition of guinea pig anti-sheep immunoglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement components were deposited in larger amounts in the clusterin depleted group. These data support a possible role for clusterin in vivo in the protection of complement-induced glomerular injury.
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PMID:Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney. 819 84

We found that TGF-beta 1 expression and increased matrix production is transient and self-limited in nephritic glomeruli from rats with acute, reversible glomerulonephritis induced by a single injection of an antibody reactive with glomerular mesangial cells. In contrast, in rats given a second antibody injection, one week later, the glomerular expression of TGF-beta 1 mRNA and TGF-beta 1 protein remained elevated through 18 weeks and was associated with a large infiltration of mononuclear cells, with staining features of fibroblastic/myofibroblastic cells, strongly expressing TGF-beta 1 in the tubulointerstitium of the kidney. By 18 weeks kidneys from animals receiving two antibody injections showed glomerulosclerosis and tubulointerstitial fibrosis with striking deposition of collagens type I and III, whereas kidney tissue from animals given one antibody injection was indistinguishable from normal control. The histological changes were accompanied by persistent proteinuria and elevated levels of blood urea nitrogen. Extracellular matrix markers of TGF-beta 1 activity, a special isoform of fibronectin, tenascin, biglycan and plasminogen activator inhibitor-1, were significantly elevated in kidneys undergoing fibrosis. These data suggest that sustained TGF-beta 1 expression contributes to the development of progressive kidney fibrosis.
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PMID:Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. 819 98

Fibronectin (FN) turnover and turnover changes induced by the anticancer drug Adriamycin (ADR) were measured in human mesangial cells (HMC) in vitro. HMC cultures synthesize cellular FN (2.2 +/- 0.3% of total protein synthesis; n = 12) which is secreted and incorporated into a fibrillar extracellular matrix (ECM). A 24 hr incubation of HMC with ADR (0.5-5 micrograms/ml) resulted in an accumulation of FN in the culture medium, with a maximum increase following 5 micrograms/ml (7.3 +/- 2.3 pg/cell vs. controls: 4.4 +/- 1.9 pg/cell; n = 10). Correspondingly, radioactively labeled immunoprecipitable FN was increased in a dosage-dependent manner in the culture medium up to 50% vs. controls. The incorporation of radioactively labeled FN into ECM was significantly increased following 2 micrograms ADR/ml. In accordance, immunofluorescence staining revealed an expansion of pericellular FN fibers in cultures exposed to 2 micrograms ADR/ml. Concomitant with the accumulation of extracellular FN, radioactively labeled FN in the cells was reduced by 22%. Qualitative characterization of FN patterns revealed a diminished number of degradation products in the culture medium of ADR-treated HMC. These data suggest that ADR interferes with the turnover of FN secreted by HMC in vitro in such a way that FN accumulates extracellularly. This in turn leads to a reduced FN synthesis. These findings are compatible with a loss of urinary FN degradation products accompanying the onset of proteinuria in ADR-treated rats.
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PMID:Fibronectin turnover in human mesangial cell cultures as affected by adriamycin. 824 31

To explore the possibility that the excretion of urinary fibronectin degradation products (U-FnDP) can be an indicator of the progression of diabetic nephropathy, U-FnDP and urinary protein(U-P) were determined in 64 diabetic patients and 11 healthy volunteers. Moreover, to determine whether continuous subcutaneous heparin infusion (CSHI) reduces elevated U-FnDP and U-P in diabetic patients with persistent proteinuria, heparin sodium was administered as a bolus subcutaneous injection of 5000 IU, followed by subcutaneous infusion of 250 IU/kg per 24 h heparin sodium for 7 days. U-FnDP excretion rate elevated proportionally to the degree of U-P. CSHI reduced significantly elevated U-FnDP from 172.68 +/- 15.79 to 100.04 +/- 14.93 micrograms/24 h (P < 0.01) and U-P from 1.76 +/- 0.13 to 1.20 +/- 0.12 g/24 h (P < 0.01). No significant changes in blood pressure and diurnal mean plasma glucose levels were found. APTT was prolonged with a decrease of AT-III activity during the treatment. These findings suggest that U-FnDP can be one of the indicators which reflects the degree of progression of diabetic nephropathy, and that CSHI may be useful for the normalization of elevated U-FnDP and reduction in U-P in diabetic nephropathy.
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PMID:Relationship between urinary excretion of fibronectin degradation products and proteinuria in diabetic patients, and their suppression after continuous subcutaneous heparin infusion. 825 24

We previously reported that lysozyme electrostatically inhibits the fibronectin-mediated DNA binding to the glomerular basement membrane (GBM) and reduces in situ DNA-anti-DNA complex formation in the GBM in NZB/W F1 mice [1]. In this study, we further noticed significant increases in urinary excretion of anti-DNA antibodies and immune complexes (IC) in lysozyme-treated NZB/W F1 mice. Their clearance ratios of IgG anti-DNA antibody to whole IgG were markedly high compared with those of saline-treated animals. A large number of IgG and C3 positive granules were observed in the tubular cells of NZB/W F1 mice treated with lysozyme. On the contrary, nil or only small amounts of anti-DNA antibodies were detected in the urine of NZB/W F1 mice without lysozyme administration despite a large amount of proteinuria, suggesting entrapment of the antibodies in lupus glomeruli. Lysozyme neither inhibited the binding of anti-DNA antibodies to DNA or heparan sulphate nor did it displace anti-DNA antibodies and IC from the kidney homogenates of lupus mice. It thus appears that the inhibition of DNA binding to the GBM due to lysozyme reduced the entrapment of anti-DNA antibodies in the GBM, resulting in urinary excretion of the antibodies.
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PMID:Specific increases in urinary excretion of anti-DNA antibodies in lupus mice induced by lysozyme administration: further evidence for DNA-anti-DNA immune complexes in the pathogenesis of nephritis. 841 71


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