Temporary effects of circulating Amadori products on glomerular filtration properties in the normal mouse

2001 ◽  
Vol 280 (1) ◽  
pp. F103-F111 ◽  
Author(s):  
I. Londoño ◽  
M. Bendayan
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Normal Mouse ◽  
Early Diabetes ◽  
Amadori Products ◽  
Time Points ◽  
Glycated Proteins ◽  
Filtration Properties

Previous studies have established a preferential glomerular filtration of glycated BSA (gBSA), as well as a facilitated filtration of BSA in the presence of gBSA. We intend to determine whether these modifications are permanent or transitory. gBSA was intravenously injected into anesthetized normal mice and maintained in circulation for 30 min, 1, 2, 24, and 48 h. Five minutes before death, FITC-BSA was injected. On immunocytochemical evaluations, increased glomerular filtration of FITC-BSA was found at all circulating time points. Changes at 24 and 48 h were less pronounced. Glomerular basement membrane (GBM)-to-lumen gBSA labeling ratios were similar at all time points suggesting no accumulation of gBSA in the GBM. Seventy percent of the gBSA was cleared from the circulation and the GBM after 24 h, and 95% after 48 h. This was confirmed in experiments with radiolabeled tracers. These results suggest that the alteration in GBM permeability to BSA in the normal mouse are due to the presence of gBSA and are gradually overcome along with its clearance from circulation. In early diabetes, increasing concentrations of circulating glycated proteins could be responsible for changes in glomerular permselectivity and probably for the alteration in glomerular filtration properties leading to diabetic nephropathy.

scholarly journals Glomerular permeability is not affected by heparan sulfate glycosaminoglycan deficiency in zebrafish embryos

2019 ◽  
Vol 317 (5) ◽  
pp. F1211-F1216 ◽  
Author(s):  
Ramzi Khalil ◽  
Reshma A. Lalai ◽  
Malgorzata I. Wiweger ◽  
Cristina M. Avramut ◽  
Abraham J. Koster ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Heparan Sulfate ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Experimental Models ◽  
Tubular Reabsorption ◽  
Glomerular Filtration Barrier ◽  
Glomerular Permeability ◽  
Tracer Injection ◽  
Filtration Barrier

Proteinuria develops when specific components in the glomerular filtration barrier have impaired function. Although the precise components involved in maintaining this barrier have not been fully identified, heparan sulfate proteoglycans are believed to play an essential role in maintaining glomerular filtration. Although in situ studies have shown that a loss of heparan sulfate glycosaminoglycans increases the permeability of the glomerular filtration barrier, recent studies using experimental models have shown that podocyte-specific deletion of heparan sulfate glycosaminoglycan assembly does not lead to proteinuria. However, tubular reabsorption of leaked proteins might have masked an increase in glomerular permeability in these models. Furthermore, not only podocytes but also glomerular endothelial cells are involved in heparan sulfate synthesis in the glomerular filtration barrier. Therefore, we investigated the effect of a global heparan sulfate glycosaminoglycan deficiency on glomerular permeability. We used a zebrafish embryo model carrying a homozygous germline mutation in the ext2 gene. Glomerular permeability was assessed with a quantitative dextran tracer injection method. In this model, we accounted for tubular reabsorption. Loss of anionic sites in the glomerular basement membrane was measured using polyethyleneimine staining. Although mutant animals had significantly fewer negatively charged areas in the glomerular basement membrane, glomerular permeability was unaffected. Moreover, heparan sulfate glycosaminoglycan-deficient embryos had morphologically intact podocyte foot processes. Glomerular filtration remains fully functional despite a global reduction of heparan sulfate.

Charge-Dependent Filtration Properties of Glomerular Basement Membrane

2015 ◽  
pp. 45-51
Author(s):  
Bo Feldt-Rasmussen ◽  
Torsten Deckert ◽  
Ren� Djurup ◽  
Marja Deckert ◽  
Lester Baker
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Filtration Properties

scholarly journals Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier

2020 ◽  
Vol 318 (6) ◽  
pp. F1520-F1530
Author(s):  
Kozue Uchio-Yamada ◽  
Keiko Yasuda ◽  
Yoko Monobe ◽  
Ken-ichi Akagi ◽  
Osamu Suzuki ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Gbm Thickening ◽  
Strain Dependent ◽  
Deficient Mice

Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that Tns2-deficient mice exhibit defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-α2 accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that Tns2 deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-α2 in podocytes. Our study suggests that weakened podocyte-GBM interaction due to Tns2 deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-α2, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier.

scholarly journals Clogging of the glomerular basement membrane.

1982 ◽  
Vol 93 (2) ◽  
pp. 489-494 ◽  
Author(s):  
Y S Kanwar ◽  
L J Rosenzweig
Keyword(s):  
Glomerular Filtration Rate ◽  
Bovine Serum Albumin ◽  
Basement Membrane ◽  
Serum Albumin ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Bovine Serum ◽  
Filtration Rate ◽  
Inulin Clearance ◽  
Selective Filter

The negative charges of the sulfated glycosaminoglycans (GAGs) of the glomerular basement membrane (GBM) were differentially neutralized by perfusin with high molarity buffers in order to determine whether or not these charges protect the GBM from being clogged by circulating plasma macromolecules. Progressive elimination of the negative charges resulted in clogging of the GBM by perfused native ferritin (NF) and bovine serum albumin as evidenced ultrastructurally by the increase in accumulation of NF in the GBM. In addition, the permeability of the GBM to 125I-insulin, a macromolecule which is normally freely permeable, and the glomerular filtration rate (as determined by [3H]inulin clearance) were markedly reduced after the GBM had been clogged with NF in the presence of high molarity buffer, thereby indicating that clogging severely reduces the ability of the GMB to act as a selective filter. These findings are consistent with the idea that the sulfated GAGs of the GBM serve as anticlogging agents.

scholarly journals Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy

Diabetologia ◽  
1995 ◽  
Vol 38 (10) ◽  
pp. 1169-1175 ◽  
Author(s):  
J. H. M. Berden ◽  
J. van den Born ◽  
A. A. van Kraats ◽  
M. A. H. Bakker ◽  
K. J. M. Assmann ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Heparan Sulphate ◽  
Anionic Sites

Renal handling of native and glycated albumins by the normal mouse

1995 ◽  
Vol 53 ◽  
pp. 948-949
Author(s):  
I. Londoño ◽  
M. Bendayan
Keyword(s):  
Diabetic Nephropathy ◽  
Normal Mouse ◽  
Protein A ◽  
Covalent Attachment ◽  
Renal Handling ◽  
Glycated Proteins ◽  
Stable Product

One of the major pathophysiological sequela of long-term hyperglycemia is the increased glycation of proteins. The glycation reaction consists in the covalent attachment of glucose molecules to amino groups in proteins forming a stable product, the Amadori adduct. Albeit further transformations can occur, Amadori adducts constitute the predominant form of circulating glycated proteins in normal and diabetic subjects, and seem to be directly involved in the pathogenesis of diabetic nephropathy.In an attempt to determine the role of glycated proteins in glomerular hyperfiltration and proteinuria characteristics of diabetic nephropathy, we have evaluated the renal handling of glycated albumins by the normal mouse, at two levels: the glomerular filtration and the tubular epithelial reabsorption. Bovine serum albumin (BSA) was glycated in vitro within conditions allowing for the formation of Amadori products. Both native and glycated albumins were tagged to haptens and intravenously injected in mice. Upon 10 and 30 min of circulation, the renal cortex was fixed and processed for immunocytochemical labeling which combined anti-hapten antibodies and protein A-gold complexes.

Sign in / Sign up

Export Citation Format

Share Document