Alterations in Glomerular Anionic Sites in Canine Anti-Glomerular Basement Membrane Nephritis with Onset of Severe Proteinuria

“…Four animals were assigned to each group. Staining of glomerular anionic sites with polyethyleneimine (PEI; molecular weight = 1,800; Wako Pure Chemical Industries, Ltd., Osaka) was performed by a minor modification of the method described by Schurer et al [13] and Sugimoto et al [14]. Freshly sampled renal cortex was cut into 0.5 mm 3 pieces and immersed in 0.5% PEI in physiological saline for 30 min at room temperature.…”

Section: Measurement Parametersmentioning

confidence: 99%

Examination of the Pathogenesis of Diabetic Nephropathy in OLETF Rats.

Kawano

Hirashima

Man

et al. 1999

The Journal of Veterinary Medical Science

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ABSTRACT. We conducted protein loading to examine the progression and pathogenesis of diabetic nephropathy. For this experiment, male OLETF, LETO, F344 and BN rats were used. This experiment was performed on rats between 5 and 30 weeks of age. Examination parameters included body weight, food intake, oral glucose tolerance test (OGTT), urinary protein level (UP), urinary albumin level (UA), glomerular filtration rate (GFR), kidney weights, light microscopy (LM) and electron microscopy (EM). In the protein-loaded OLETF group, the UP level was markedly increased 20 weeks or more after birth. In OLETF control group, GFR were higher than those in other strains. Glomerular hypertrophy and kidney weights were markedly increased in protein-loaded groups in OLETF rats. Thirty weeks after birth, EM showed that the number of polyethyleneimine (PEI) of the glomerular basement membrane (GBM) in protein-loaded OLETF group was significantly decreased compared to that in control group. These changes in OLETF rats were more marked in the proteinloaded group than those in the control group. LM showed that the number of exudative lesions with fibrin-cap in the protein-loaded OLETF group was significantly increased than those in control group. In OLETF rats, protein loading caused deterioration of nephropathy at 30 weeks of age. Therefore, it was demonstrated that not only blood sugar control but also protein intake factors play important roles in the deterioration of nephropathy in OLETF rats.-KEY WORDS: diabetes, nephropathy, OLETF, protein, rat.J. Vet. Med. Sci. 61(11): 1219-1228, 1999 nephropathy did not differ from that in untreated OLETF rats [8,9]. As a factor in this finding, food intake and protein intakes were decreased because sucrose-loaded rats liked to ingest sucrose. The decrease in protein intake may have influenced deterioration of nephropathy. Furthermore, in humans, it has been reported that a protein-restricted diet is effective in treating diabetic nephropathy. Therefore, we speculated that there might be an association between deterioration of diabetic nephropathy and protein intake. In this study, we performed protein loading in OLETF rats, and examined the involvement of protein in deterioration of diabetic nephropathy. MATERIALS AND METHODS Establishment of experimental groupsWe used male OLETF and LETO rats bred at the Tokushima Research Institute of Otsuka Pharmaceutical Co., Ltd. as well as F344 and BN rats purchased from Charles River Japan Inc. (Yokohama). In all strains, we established control groups in which standard chow (CRF-1; Oriental Yeast Co., Ltd., containing 23% crude protein) was given and 40% protein-loaded groups (40% crude protein was contained in food). The food composition was shown in Table 1. Eight animals were assigned to each group. This experiment was conducted in rats between 5 and 30 weeks of age. Animals were acclimated in the specific pathogenfree (SPF) room under the following conditions; temperature, 23 ± 2°C; humidity, 60 ± 10%; and lighting cycle, 12 hr (7:00 a.m. to 7:00 ...

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“…In contrast, ASs in LRI are relatively few and distributed irregularly, as reported in the rat [1,14,26], dog [20] and human kidneys [22]. Therefore, we assessed ASs only in the LRE of the GBM in this study.…”

Section: Discussionmentioning

confidence: 98%

“…The glomerular ASs are mainly composed of heparan sulphate proteoglycan (HSPG) which is one of the major constituents of the GBM [10]. Immunohistochemical studies have revealed no diminution in glomerular staining of HSPG in human diabetic glomerulosclerosis [30], human glomerulonephritis [7] and nephrotoxic nephritis in dogs [20]. In contrast, a structural alteration of HSPG has been suggested to explain the loss of charge selectivity resulting in proteinuria [9].…”

Section: Discussionmentioning

confidence: 99%

“…Rabbits received a single intravenous injection of cationized protein developed a transient interaction of the protein with fixed ASs in the glomerular basement membrane (GBM) resulting in loss of negative charge and concomitant proteinuria [2]. Recent studies have shown that the number of ASs in the GBM decreases in some human glomerulonephropathies [4,11,24,27,28] and experimental nephropathies [1,8,13,20,21,25,26]. It is interesting to note that in experimentally induced acute serum sickness of rabbits, cationic proteins derived from platelets and neutrophils may bind to glomerular capillary walls and possibly contribute to the neutralization of glomerular polyanions [3].…”

Section: Histopathologymentioning

confidence: 99%

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Alteration of Anionic Sites in Renal Glomerular Basement Membrane of Pigs.

et al. 1997

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ABSTRACT. Ultrastructural alteration of anionic sites (ASs) in the glomerular basement membrane (GBM) was studied in 10 cases of swine mesangial proliferative glomerulonephritis using a cationic ultrastructural tracer, 0.5% polyethyleneimine (M.W.= 1,800). Glomerular ASs were seen as discrete electron-dense particles in the GBM, mesangial matrix and epithelial cell surfaces by electron microscopy. In the lamina rara externa (LRE) of the normal GBM, ASs were distributed regularly in a single layer. In those areas of the LRE that contained electron dense deposits or clusters of spherical microparticles (SMPs), however, a distinct reduction or loss of ASs was observed in all the pigs. Quantitative assessment of ASs in the LRE over 1,000 nm of the GBM revealed a significant reduction in ASs in one case with diffuse global thickening of the GBM as compared with the remaining nine pigs without GBM thickening (P<0.001, MannWhitney's U-test). There were no ASs in the lamina densa (LD) of the normal GBM, but an irregular distribution of ASs was seen within the LD of the pig showing diffuse global thickening of the GBM. These results suggest that a disturbance of the charge-selective barrier in the GBM may be induced by electron-dense deposits or SMPs in the LRE as well as thickening of the GBM in swine glomerulonephritis. -KEY WORDS: anionic site, glomerular basement membrane, glomerulonephritis, kidney, swine.

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Alterations in Glomerular Anionic Sites in Canine Anti-Glomerular Basement Membrane Nephritis with Onset of Severe Proteinuria

Cited by 6 publications

References 19 publications

Ultrastructural and functional analyses of nephropathy in calmodulin‐induced diabetic transgenic mice

Ultrastructural and functional analyses of nephropathy in calmodulin‐induced diabetic transgenic mice

Examination of the Pathogenesis of Diabetic Nephropathy in OLETF Rats.

Alteration of Anionic Sites in Renal Glomerular Basement Membrane of Pigs.

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