In vivo studies on basement membrane synthesis in diabetic and nondiabetic rats

Hasslacher, C; Kopischke, H. G.; Bürklin, E.; Gechter, F.; Reichenbacher, R.

doi:10.1007/bf01851197

Cited by 18 publications

(8 citation statements)

References 9 publications

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“…In this context, the serum and/or u-IV collagen levels had been proposed as candidate for the indicator on the grounds that the accumulation of extracellular matrix (ECM) components such as type IV collagen is a characteristic glomerular pathological change associated with NIDDM [5, 6, 15, 16, 17, 18, 19]. Studies intended to confirm a high degree of correlation between the serum level and the urinary excretion of type IV collagen and the nephropathy in patients with diabetes have yielded conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Type IV Collagen as a Specific Indicator of the Progression of Diabetic Nephropathy

Watanabe

Sanada

Shigetomi

et al. 2000

Nephron

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Aims and Methods: This study was carried out to clarify whether the urinary excretion of type IV collagen (u-IV collagen) detected by specific radioimmunoassay, can be used as an indicator for the progression of diabetic nephropathy. Results: u-IV collagen was higher in diabetic subjects with microalbuminuria and overt proteinuria than those with normoalbuminuria, IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, or control normal subjects. u-IV collagen was positively correlated with serum and urinary β₂-microglobulin and negatively with creatinine clearance only in diabetic patients, but not in patients with other glomerular diseases. The serum type IV collagen was not different between all the groups, and not correlated with its urinary excretion. In the advanced diabetic nephropathy, immunoreactive type IV collagen was detected in glomerular basement membrane (GBM), tubular basement membrane and Bowman’s capsule much more than that in the normal kidney. Conclusion: These findings indicated increased production and degeneration of type IV collagen in diabetic nephropathy. It is suggested that augmented turnover of type IV collagen in GBM and tubular basement membrane results in increased concentrations of free u-IV collagen. Therefore, measurement of u-IV collagen may be a useful, specific indicator of the progression of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Type IV Collagen as a Specific Indicator of the Progression of Diabetic Nephropathy

Watanabe

Sanada

Shigetomi

et al. 2000

Nephron

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“…However, efforts to define the basis for altered basement membrane metabolism are inconclusive. Collagen synthesis is reported to be increased in glomeruli isolated from short-term diabetic rats (6,7), whereas rats with chronic diabetes have unchanged collagen production (8). Similarly, synthesis of basement membrane proteoglycans monitored by [ 35 S]sulfate incorporation suggests reduced synthesis in diabetic glomeruli (9,10), but at least one study with similar procedures attributed reduced proteoglycan content to altered turnover (11).…”

mentioning

confidence: 92%

Altered Steady-State mRNA Levels of Basement Membrane Proteins in Diabetic Mouse Kidneys and Thromboxane Synthase Inhibition

et al. 1990

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We examined steady-state levels of mRNA encoding type IV collagen, B1 chain of laminin, and the basement membrane heparan sulfate proteoglycan in the kidney cortex of a mouse model (KKAy) of non-insulin-dependent diabetes. mRNAs encoding laminin B1 and the proteoglycan were unchanged in kidneys taken from diabetic mice with demonstrable basement membrane thickening. mRNA levels for type IV collagen, in contrast, were significantly elevated (2-fold) in diabetic mice concurrent with but not preceding morphologically thickened basement membranes. There was a negative correlation between a ratio of proteoglycan/type IV collagen and levels of albuminuria in the diabetic mice. No correlation was noted with laminin. We also examined the effects of inhibiting the synthesis of thromboxane, a potent vasoconstrictor, on the steady-state levels of type IV collagen in the diabetic mice. Inhibition of thromboxane stopped the progression of albuminuria and prevented an increase in type IV collagen mRNA levels. We conclude that basement membrane thickening in diabetes, a hallmark of diabetic nephropathy, is partly a consequence of an unbalanced increase in the production of type IV collagen. The relative decrease in proteoglycan production may contribute to chronic albuminuria.

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“…Collagen synthesis has been reported to increase in the glomeruli isolated from rats with short-term diabetes (1,2). Previous studies on the basement membrane in diabetes indicated that the production of its components is altered.…”

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confidence: 99%

ECM Gene Expression and Its Modulation by Insulin in Diabetic Rats

et al. 1992

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The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.

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In vivo studies on basement membrane synthesis in diabetic and nondiabetic rats

Cited by 18 publications

References 9 publications

Urinary Excretion of Type IV Collagen as a Specific Indicator of the Progression of Diabetic Nephropathy

Urinary Excretion of Type IV Collagen as a Specific Indicator of the Progression of Diabetic Nephropathy

Altered Steady-State mRNA Levels of Basement Membrane Proteins in Diabetic Mouse Kidneys and Thromboxane Synthase Inhibition

ECM Gene Expression and Its Modulation by Insulin in Diabetic Rats

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