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)

The changes in glomerular extracellular matrices components in diabetic nephropathy were investigated. Indirect immunofluorescence staining, using polyclonal antibodies to heparan sulfate proteoglycan (HS-PG), laminin, type IV collagen, and fibronectin was carried out on renal specimens obtained by needle biopsy. Immunofluorescence intensity and distribution were observed. HS-PG and laminin decreased in the capillary walls; on the other hand, type IV collagen and fibronectin tended to increase in the mesangial area. HS-PG and laminin decreased in inverse proportion to sclerosis grades and proteinuria. These changes seemed to play an important role in progression of diabetic glomerulosclerosis.
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PMID:Changes in glomerular extracellular matrices components in diabetic nephropathy. 177 41

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

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

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

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

We analyzed the composition of the extracellular matrix in the glomeruli from 31 cases with different degrees of diabetic nephropathy by immunohistochemical means. While the enlarged mesangial matrix in diffuse glomerulosclerosis showed an increased staining reaction for the basement membrane components collagen IV and V, laminin and fibronectin, the staining pattern of the basement membrane associated heparan sulfate proteoglycan (HSPG) was markedly reduced. Early, small nodular lesions in diabetic glomeruli were similarly positive for most of the basement membrane (BM)-components, while HSPG remained absent. With an increase in the diameter of the noduli, however, the staining reaction for the BM-components diminished, while interstitial collagens V and III were present in these noduli in substantial amounts. Our findings 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 morphological correlate to the impaired filter function of the glomerular BM, while the occurrence of interstitial collagens within the glomeruli in late nodular stages may be regarded as the result of an altered pattern of expression of the mesangial cells.
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PMID:[Immunohistochemical localization of various components of the basal membrane and interstitial collagen in diabetic nephropathy]. 248 99

This study was undertaken to elucidate the distributions of laminin, fibronectin, type I, III, IV, V and VI collagen and heparan sulfate proteoglycan (HSPG) in diabetic nephropathy, using immunohistochemical procedures. The pathological features of diabetic glomerulosclerosis were characterized as diffuse and nodular lesions, showing an expanded mesangial matrix associated with a thickened glomerular basement membrane (GBM). In the thickened GBM, laminin was present throughout the whole membrane, type IV collagen occurred along the subendothelial side, and HSPG was present with no change in its amount. On the other hand, the components detected in the slightly expanded mesangial matrix were type IV, V and VI collagen, fibronectin and HSPG, but not laminin. When the matrix was expanded markedly, collagenous components were increased over the other components. In the typical Kimmelstiel-Wilson nodules, the mesangial matrix was occupied mainly by type V and VI collagen with a relative decrease in type IV collagen. When a nodular lesion adhered to Bowman's capsule, type I and III collagen occurred not only in Bowman's space but also within the lesion itself. Furthermore, laminin and HSPG became detectable on the outside of the lesion, but not within it. These results suggested that there was a difference in the distribution and proportion of extracellular matrix components between diffuse and nodular lesions. It appeared that the nodular lesion was not simply an advanced form of the diffuse lesion.
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PMID:Constituents of the extracellular matrices in diabetic glomerulosclerosis. 261 16

Diabetic nephropathy develops in many diabetic patients as consequence of glomerulosclerosis. On the basis of a series of recent observations it is suggested that a combination of metabolic and hemodynamic changes is responsible for the pathogenesis of diabetic nephropathy. Since the glomerular filtration unit has been characterized to consist of collagen type IV and minor components like laminin, fibronectin and heparan sulfate proteoglycan, influence of diabetes on basement membrane (BM) components has been studied. Biochemical alterations of glomerular BM consist of an increased nonenzymatic glucosylation of type IV collagen leading to unphysiological crosslinking. This, in turn, may result in alteration of the size selective properties of the glomerular filtration unit. Changes in composition of glomerular BM have recently been described. An increased synthesis of type IV collagen with concomitant decrease of heparan sulfate proteoglycan may lead to alteration of the charge selective barrier and consequently to increased permeability of the glomerular BM. Permanently unbalanced synthesis of BM components finally results in obliteration of the capillary lumen. In late state nephropathy intrinsic basement membrane components are no longer produced. Instead, massive accumulation of PAS positive material occurs.
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PMID:Pathobiochemical aspects of diabetic nephropathy. 297 77

We have previously reported that incubation of rat glomerular epithelial cells in vitro for 8 days with 30 mM glucose without insulin results in reduction in the synthesis of a cell layer heparan sulfate proteoglycan (HSPG) species that has hydrodynamic size and antigenic characteristics of glomerular basement membrane HSPG (1994, Arch. Biochem. Biophys 309, 149-159). In these studies, reduction in HSPG synthesis could be attributed either to high-glucose medium or to insulin deficiency. In this study we investigated the effects of insulin replacement on changes in glomerular epithelial cell metabolism of glycoconjugates induced by high-glucose medium. Addition of pharmacologic concentrations of insulin prevented the following changes induced by 30 mM glucose: (a) increment in 35SO4 incorporation into macromolecules in cell layer and medium, (b) increment in the synthesis of low anionic macromolecules, probably glycoproteins, in both cell layer and medium, (c) increment in synthesis of small-sized glycosaminoglycans (Kav 0.75 on Sephrose CL-4B) associated with the cell layer. Insulin was unable to correct the 30 mM glucose-induced reduction in the synthesis of cell layer HSPG that resembles glomerular basement membrane HSPG. Physiologic concentrations of insulin did not affect any of the changes in glycopeptide metabolism induced by 30 mM glucose. These findings suggest that (a) inhibition of glomerular epithelial cell synthesis of 35SO4-labeled low anionic macromolecules, probably glycoproteins, may be involved in insulin-induced reversal of glomerular hypertrophy seen in early diabetes, and (b) mechanisms other than insulin lack are involved in reduction in the synthesis of glomerular basement membrane HSPG in diabetic nephropathy.
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PMID:Effect of insulin on high-glucose medium-induced changes in rat glomerular epithelial cell metabolism of glycoconjugates. 773 56

In diabetic nephropathy the heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane (GBM) is reduced but the cellular mechanisms involved have not been studied. Glomerular epithelial cells (GEC) are thought to be the source of HSPG present in the GBM. In this study we examined if proteoglycan metabolism of the rat GEC in culture is dysregulated in a metabolic environment simulating diabetes. Following incubation for 8 days with a serum-supplemented medium containing 30 mM glucose and no added insulin, a significant increase in the overall synthesis of 35SO4-labeled molecules by the GEC was seen compared to control monolayers incubated with medium containing 5 mM glucose and insulin. Ion exchange chromatography revealed that 30 mM glucose did not alter the anionic charge density of proteoglycans, but significantly increased the amount of 35S-labeled low-anionic macromolecules in the medium; mannitol induced similar changes. Sepharose CL-4B chromatography, glycosaminoglycan analysis and immunoprecipitation of control cell layer proteoglycans demonstrated the presence of HSPG of hydrodynamic size, Kav 0.4, resembling rat GBM HSPG in size and antigenic nature. Incubation of GEC with 30 mM glucose resulted in a significant reduction (58%) in this HSPG species, an effect not seen with equimolar mannitol. Additionally, 30 mM glucose induced a significant increment in synthesis of a small HS species (Kav 0.71 on Sepharose CL-4B column) present in the cell layer. Our findings suggest that both osmotic and nonosmotic mechanisms are operative in dysregulation of glycopeptide metabolism by high-glucose medium and that reduced synthesis by the GEC may contribute to decreased content of GBM HSPG in diabetic nephropathy.
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PMID:Regulation of rat glomerular epithelial cell proteoglycans by high-glucose medium. 811 3


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