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)

We measured serum and urinary concentrations of type IV collagen by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in diabetics. Serum and urinary concentrations of type IV collagen measured by RIA and ELISA were increased compared to those of control subjects. In diabetics with macroproteinuria or with renal insufficiency, serum and urinary concentrations of type IV collagen were higher than in diabetics without nephropathy or with early renal damage as determined by the presence of microproteinuria. These results suggest that serum and urinary concentrations of type IV collagen are increased in patients with advanced diabetic nephropathy. These increases may indicate that alteration of basement membrane metabolism has occurred in diabetics.
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PMID:Increased concentrations of the basement membrane component type IV collagen in sera and urine of diabetics. 177 45

In order to clarify considerable alterations of the extracellular matrix components in various renal diseases, monoclonal antibodies against type IV collagen (IV col), 200-KD laminin (200-KD Lam), 400-KD laminin (400-KD Lam) and heparan sulfate proteoglycan (HSPG) were applied to 142 renal biopsy specimens for the indirect immunofluorescence. These subjects included 5 cases with 1 hour specimen in the transplanted kidney, 32 minimal change nephrotic syndrome (MCNS), 30 mesangial proliferative glomerulonephritis (PGN), 2 focal segmental glomerulosclerosis (FGS), 21 membranous nephropathy (MN), 9 membranoproliferative glomerulonephritis (MPGN), 2 poststreptococcal acute glomerulonephritis (PSAGN), 13 diabetic nephropathy (DN), 16 lupus nephritis (LN), 9 diffuse sclerosing glomerulonephritis (DSGN), 2 amyloid kidney and 1 granulomatous nephropathy in sarcoidosis. In the transplanted kidney, the staining intensity of IV col was stronger than that of 200-KD Lam, 400-KD Lam and HSPG in general. IV col was predominantly distributed throughout the mesangium area and less along the glomerular basement membrane (GBM). The positive stainings with 200-KD Lam along the GBM and that with 400-KD Lam in the mesangium area were weakly recognized. HSPG was mainly detected along the GBM in the linear fashion. In MCNS, the distribution of the extracellular matrix components was mostly identical to that in the transplanted kidney. In the group of the glomerulonephritis showed the proliferations of mesangial cells, such as PGN and MPGN, the staining intensity of both IV col and 400-KD Lam, particularly in the latter, was remarkably increased in the sclerotic lesions. In MN, the thickened GBM was strongly stained with both IV col and 200-KD Lam, and the stainings of 200-KD Lam were more intensive. And still more, by the double labelling method performed for the couple of IV col and immunoglobulins, the correlation between glomerular capillary walls and/or mesangial areas and immunoglobulins deposits became more clear. These findings suggest as follows: (1) both IV col and 400-KD Lam, in particular 400-KD Lam, are possibly involved in the process of glomerulosclerosis: (2) both IV col and 200-KD Lam, in particular 200-KD Lam, are greatly involved in the process of new basement membrane-like materials formation in MN.
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PMID:[Immunohistochemical study on the extracellular matrix components in various renal diseases]. 177 Jun 26

This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.
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PMID:Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. 183 97

The immunohistochemical localization of the extracellular matrix was examined in 31 cases with different degrees of human diabetic nephropathy using antisera to human collagen types I, III, IV, V, fibronectin, laminin, and basement-membrane-associated heparan sulfate proteoglycan (HSPG). In normal glomeruli, HSPG was predominantly localized in the glomerular basement membrane and in the mesangium, and to minor extent in the basement membranes of tubules and Bowman's capsule. Collagen IV and laminin were distributed in glomerular basement membrane and mesangium in minor amounts. Interstitial collagens usually do not occur within glomeruli except for collagen V which has a light microscopic glomerular distribution similar to collagen IV. In diabetic diffuse glomerulosclerosis, the enlarged mesangial matrix showed an increased staining reaction for collagen IV, V, laminin, and fibronectin whereas the staining pattern of HSPG was markedly reduced. Early, small nodular lesions in diabetic glomeruli were similarly positive for most of the basement membrane components, whereas HSPG remained absent. With an increase in the diameter of the noduli, however, the staining reaction for all basement membrane components diminished, whereas interstitial collagens V and III, but not collagen I, were present in these noduli in substantial amounts. These initial studies provide evidence that the changes in the glomerular matrix in diabetic nephropathy may be divided into distinct and progressing stages of lesions. The reduced amount of HSPG even in slight, early lesions may represent the morphologic correlate to the impaired filter function of the glomerular basement membrane.
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PMID:Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions. 192 5

Serum and urinary concentrations of NCl, the non collagenous globular domain of collagen IV, were used as markers for turnover of basement membranes. NCl levels were studied in membranous glomerulonephritis and diabetic nephropathy. Thirteen patients with membranous glomerulonephritis and 8 insulin-dependent diabetic patients with diabetic nephropathy were compared to 16 apparently healthy control subjects. The patients with membranous glomerulonephritis had lower levels of NCl in serum and urine compared to the control subjects. In comparison, the patients with diabetic nephropathy had similar levels of NCl in serum and urine as the control subjects. Furthermore, among patients with membranous glomerulonephritis, those with hypertension had higher serum levels of NCl than those without, which may indicate that hemodynamic factors influence the basement membrane collagen metabolism. It is suggested that there are differences in basement membrane turnover in membranous glomerulonephritis and diabetic nephropathy although there are similarities in glomerular histopathological features. Other possible mechanism are discussed. Further studies are needed to confirm the suggested mechanism.
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PMID:Urine and serum levels of the carboxyterminal domain (NCl) of collagen IV in membranous glomerulonephritis and diabetic nephropathy. 194 30

Diabetic nephropathy is characterized by progressive expansion of mesangial matrix and thickening of the glomerular basement membrane (GBM). Kidney tissues from 13 patients with insulin-dependent diabetes mellitus were studied by immunohistochemical techniques for the distribution of three recently described collagen peptides (M28+, M28 [Good-pasture antigen], and Alport antigen) and various components of classical type IV collagen [alpha 1(IV) noncollagenous (NC) globular domain, alpha 2(IV) NC, 7S, triple helix]. Recently M28 and M28+ were designated as NC monomers of alpha 3(IV) and alpha 4(IV) based on limited amino acid sequencing. During the course of the disease, the distribution of the M28 chains and the Alport peptide segregated completely from that of classical type IV collagen. In diabetic kidneys, antibodies to the M28 and Alport peptides reacted intensely with the thickened GBM but not with the mesangium. In contrast, the reactivity of antibodies to various components of classical type IV collagen was prominent within the expanded mesangial matrix with significant decrease in reactivity in the peripheral capillary wall. In hyalinized glomeruli, components of classical type IV collagen virtually disappeared, whereas the M28 and Alport peptides persisted in the collapsed GBM. These studies support the view that expansion of the mesangial matrix and thickening of the GBM involve separate and distinct collagen components. The differential expression of the M28 and Alport peptides compared with that of classical type IV collagen may be a consequence of differing sites of synthesis (classical type IV collagen from endothelial/mesangial cells and M28 and Alport chains from visceral epithelial cells), independent control mechanisms, and/or differences in degradation.
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PMID:Differential expression of basement membrane collagen chains in diabetic nephropathy. 199 66

Nodular expansion of glomerular mesangium with increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular mesangium, accumulate 50-60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulse-chase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S [( 35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were examined, and degradation rates were estimated from the disappearance of radioactivity from matrix proteins in mesangial cells previously incubated with Trans-35S. One week of growth in 30 mM glucose resulted in approximately 40-50% increase in the synthesis of all three matrix proteins compared with 10 mM glucose-grown cells. This was accompanied by a significant increase in the transcripts for all three matrix proteins (approximately twofold). The specific activity of the radiolabel in trichloroacetic acid-precipitable cell protein showed no difference between cells grown in 10 or 30 mM glucose, indicating that total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV collagen degradation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium. 199 70

Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis.
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PMID:Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels. 202 27

In order to study the localization of Lentil lectin (LCH)-binding glycoresidues in glomeruli from patients with a variety of glomerulopathies, and to elucidate the relationship between LCH-binding sugars and the components of the extracellular matrix, laminin and type IV collagen, investigations of formalin-fixed, paraffin-embedded kidney tissues digested with trypsin were carried out by the direct and indirect immunofluorescence microscopy techniques. The glomerular basement membrane (GBM) and the mesangium reacted well with LCH, whereas areas with sclerotic lesions exhibited a decreased reactivity. The pattern of LCH binding to the GBM in various glomerulopathies was similar to that of laminin but different from that of type IV collagen. The pattern of localization of LCH-reacting sites and of laminin in the GBM included the double linear lines in diabetic nephropathy, inner linear line with outer projections (spikes) in membranous nephropathy, and reduplicated basement membrane in membranoproliferative glomerulonephritis. The results obtained by enzyme-linked immunoadsorbent assay showed that LCH had a stronger reactivity for laminin than for type IV collagen or fibronectin. These findings suggest that LCH is more reactive with laminin than with other components of the glomerular extracellular matrix.
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PMID:Histochemical and immunohistochemical studies of diseased human glomeruli. 203 28

Glomerular basement membrane (GBM) thickening has been reported to be a characteristic change of diabetic nephropathy. Previous studies of GBM in animal models of diabetes indicated that there are no consensus in the alteration of synthesis of GBM component. The aim of this study was to determine whether the glomerular mRNA levels encoding type I and type IV collagen. B1 laminin, and heparan sulfate proteoglycan (HSPG) are altered in streptozotocin diabetic rats with or without insulin therapy. Glomerular mRNA levels for type I and type IV collagen, laminin B1, were significantly increased, but that for HSPG were marked decreased in 4 week diabetic rats compared with age-matched control rats. Insulin therapy has normalized these abnormally regulated gene expressions. Renal morphology shows no significant changes between 4 weeks diabetic rats and age-matched control rats. These results indicate that abnormal gene expressions of BM components and type I collagen might play an important role in the initiation of glomerular changes in diabetes.
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PMID:[Altered glomerular mRNA expression of basement membrane components and type I collagen in diabetic rats treated with or without insulin therapy]. 206 13


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