Glomerular basement membrane synthesis and serum concentration of type IV collagen in streptozotocin-diabetic rats

Hasslacher, C; Reichenbacher, R.; Gechter, F.; Timpl, Rupert

doi:10.1007/bf00281124

Cited by 59 publications

(14 citation statements)

References 19 publications

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“…The serum levels of both 7S collagen and laminin PI were significantly elevated. The results agree with recently published animal trials [17], The patients with microvascular damage showed a higher increase than those without microangiopathy.…”

Section: Discussionsupporting

confidence: 83%

Basement Membrane Components (7S Collagen, Laminin PI) Are Increased in Sera of Diabetics and Activate Platelets in vitro

Högemann¹,

Balleisen²,

Rauterberg

et al. 1986

Pathophysiol Haemos Thromb

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Serum concentrations of two basement membrane components (7S collagen and laminin P1) were detected by specific radioimmunoassays in 70 patients suffering from diabetes mellitus type I and II with and without clinical signs of microangiopathy. Serum levels of both antigens were increased compared to controls. 7S collagen concentrations were significantly different between the diabetics with signs of microvascular damage and those without small-vessel disease (p < 0.05). Laminin P1 concentrations were also elevated, but the difference between the two groups of diabetics was not significant (p < 0.2). Raised levels of circulating basement membrane proteins may indicate connective tissue activity and development of diabetic microangiopathy. In vitro 7S collagen is a moderate platelet activator inducing platelet spreading, aggregation, and malondialdehyde production. Laminin activates platelet spreading. As a part of the altered hemostatic system the activation of basement membrane components may contribute to the development of microvascular damage.

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Section: Discussionsupporting

confidence: 83%

Basement Membrane Components (7S Collagen, Laminin PI) Are Increased in Sera of Diabetics and Activate Platelets in vitro

Högemann¹,

Balleisen²,

Rauterberg

et al. 1986

Pathophysiol Haemos Thromb

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show abstract

“…Its deleterious effects are attributable to the formation of sugarderived protein adducts and cross-links known as AGE. Exposure of cultured mesangial cells to AGE results in a receptormediated up-regulation of mRNA and protein secretion of Col4 (4,32). We have previously shown that AGE/RAGE system is critical for progression of glomerulosclerosis, as shown in the study AGE breaker and RAGE knock-out mice (25,(33)(34)(35).…”

Section: Discussionmentioning

confidence: 89%

Activation of Bone Morphogenetic Protein 4 Signaling Leads to Glomerulosclerosis That Mimics Diabetic Nephropathy

Tominaga

Abe

Ueda³

et al. 2011

Journal of Biological Chemistry

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Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. We have previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix (ECM) proteins in DN. However, little is known about the regulatory mechanisms that induce and activate Smad1. Here, bone morphogenetic protein 4 (Bmp4) was found to up-regulate the expression of Smad1 in mesangial cells and subsequently to phosphorylate Smad1 downstream of the advanced glycation end product-receptor for advanced glycation end product signaling pathway. Moreover, Bmp4 utilized Alk3 and affected the activation of Smad1 and Col4 expressions in mesangial cells. In the diabetic mouse, Bmp4 was remarkably activated in the glomeruli, and the mesangial area was expanded. To elucidate the direct function of Bmp4 action in the kidneys, we generated transgenic mice inducible for the expression of Bmp4. Tamoxifen treatment dramatically induced the expression of Bmp4, especially in the glomeruli of the mice. Notably, in the nondiabetic condition, the mice exhibited not only an expansion of the mesangial area and thickening of the basement membrane but also remarkable albuminuria, which are consistent with the distinct glomerular injuries in DN. ECM protein overexpression and activation of Smad1 in the glomeruli were also observed in the mice. The mesangial expansion in the mice was significantly correlated with albuminuria. Furthermore, the heterozygous Bmp4 knock-out mice inhibited the glomerular injuries compared with wild type mice in diabetic conditions. Here, we show that BMP4 may act as an upstream regulatory molecule for the process of ECM accumulation in DN and thereby reveals a new aspect of the molecular mechanisms involved in DN.

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“…Furthermore, metabolic studies in experimental animals have provided evidence that enhanced production of collagen is a central event in the development of the diabetic glomerular extracellular matrix abnormality (4,5).…”

mentioning

confidence: 99%

Occurrence of Type VI Collagen in Extracellular Matrix of Renal Glomeruli and Its Increase in Diabetes

1990

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Human and bovine glomerular basement membrane (GBM) preparations, representing the extracellular matrix of the renal filtration units, were found to contain type VI collagen. This protein was solubilized by guanidine and guanidine-dithiothreitol extractions and characterized after polyacrylamide gel electrophoretic resolution by immunoblotting with an antiserum directed against the alpha 1(VI) and alpha 2(VI) polypeptide chains and by its insensitivity to collagenase digestion in the nonreduced state. In contrast to GBM, which is the product of three distinct cells, type VI collagen could not be detected in extracts from calf lens capsule, an epithelial cell-derived basement membrane. Quantitation by radioimmunoassay of the type VI collagen content of GBM from 17 diabetic and 15 nondiabetic human subjects indicated a 2.8-fold higher level (P less than 0.001) in the diabetic preparations. Because in the glomerulus type VI collagen is considered on the basis of immunohistochemistry to be localized to the mesangium, we believe that measurement of this protein in GBM preparations can provide a valuable index of mesangial expansion in diabetic and other glomerulopathies.

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Glomerular basement membrane synthesis and serum concentration of type IV collagen in streptozotocin-diabetic rats

Cited by 59 publications

References 19 publications

Basement Membrane Components (7S Collagen, Laminin PI) Are Increased in Sera of Diabetics and Activate Platelets in vitro

Basement Membrane Components (7S Collagen, Laminin PI) Are Increased in Sera of Diabetics and Activate Platelets in vitro

Activation of Bone Morphogenetic Protein 4 Signaling Leads to Glomerulosclerosis That Mimics Diabetic Nephropathy

Occurrence of Type VI Collagen in Extracellular Matrix of Renal Glomeruli and Its Increase in Diabetes

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