Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter

2011 ◽  
Vol 300 (4) ◽  
pp. F848-F856 ◽  
Author(s):  
Sahoko Sekiguchi ◽  
Atsushi Suzuki ◽  
Shogo Asano ◽  
Keiko Nishiwaki-Yasuda ◽  
Megumi Shibata ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Connexin 43 ◽  
Chronic Renal Disease ◽  
Rat Kidney ◽  
Cellular Damage ◽  
Glomerular Sclerosis ◽  
Wild Type ◽  
Podocyte Injury ◽  
Type Iii

Uptake of Pi at the cellular membrane is essential for the maintenance of cell viability. However, phosphate overload is also stressful for cells and can result in cellular damage. In the present study, we investigated the effects of the transgenic overexpression of type III Pi transporter Pit-1 to explore the role of extracellular Pi in glomerular sclerosis during chronic renal disease. Pit-1 transgenic (TG) rats showed progressive proteinuria associated with hypoalbuminemia and dyslipidemia. Ultrastructural analysis of TG rat kidney by transmission electron microscopy showed a diffuse effacement of the foot processes of podocytes and a thickening of the glomerular basement membrane, which were progressively exhibited since 8 wk after birth. TG rats died at 32 wk of age due to cachexia. At this time, more thickening of the glomerular basement membrane and segmental sclerosis were observed in glomeruli of the TG rats. Immunohistochemical examination using anti-connexin 43 and anti-desmin antibodies suggested the progressive injury of podocytes in TG rats. TG rats showed higher Pi uptake in podocytes than wild-type rats, especially under low Pi concentration. When 8-wk-old wild-type and TG rats were fed a 0.6% normal phosphate (NP) or 1.2% phosphate (HP) diet for 12 wk, HP diet-treated TG rats showed more progressive proteinuria and higher serum creatinine levels than NP diet-treated TG rats. In conclusion, our findings suggest that overexpression of Pit-1 in rats induces phosphate-dependent podocyte injury and damage to the glomerular barrier, which result in the progression of glomerular sclerosis in the kidney.

scholarly journals Anionic charge concentration of rat kidney glomeruli and glomerular basement membrane

1993 ◽  
Vol 289 (3) ◽  
pp. 647-652 ◽  
Author(s):  
W D Comper ◽  
A S N Lee ◽  
M Tay ◽  
Y Adal
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Electrostatic Interactions ◽  
Enzyme Inhibitors ◽  
Rat Kidney ◽  
Basement Membranes ◽  
Sulphate Content ◽  
Anionic Charge ◽  
Charge Concentration ◽  
A Charge

Estimates of levels of glomerular and glomerular-basement-membrane anion charge should serve as useful quantitative markers for the integrity of the tissues in health and disease. We have developed a simple, rapid, technique to measure this charge through the use of ion exchange with radioisotopes 22Na+ and 36Cl- at low ionic strengths in phosphate buffer. When this technique is used, normal glomeruli isolated from rat have a measured net anion charge concentration of 17.4 +/- 3.7 p-equiv. per glomerulus (n = 20). Perfused rat kidneys that lose approximately half of their glomerular heparan [35S]sulphate content (owing to oxygen-radical damage) exhibited a lower anion charge, of 7.5 +/- 1.6 p-equiv. per glomerulus (n = 5). Glomerular basement membranes prepared from rat glomeruli by a sonication-centrifugation procedure in the presence of enzyme inhibitors had a charge concentration of 6.3 +/- 0.7 mu-equiv./g wet wt. of tissue (n = 4), whereas membranes prepared by sonication, centrifugation, DNAse and detergent treatment had a charge concentration of 7.1 +/- 1.6 mu-equiv./g wet wt. (n = 4). Isotope-dilution experiments with 3H2O on these detergent-prepared glomerular basement membranes demonstrated that they had a water content of approx. 93%, which would then give a net anion charge concentration of 7.6 +/- 1.7 m-equiv./l (n = 4). These values are in good agreement with those obtained by others using titration techniques [Bray and Robinson (1984) Kidney Int. 25, 527-533]. The relatively low magnitude of glomerular anion charge in normal kidneys is consistent with other recent findings that glomerular anion charge is too low to affect the glomerular transport of charged molecules in a direct, passive, biophysical manner through electrostatic interactions.

scholarly journals The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135648 ◽  
Author(s):  
Haiyan Wang ◽  
Zhihui Yue ◽  
Jinlang Wu ◽  
Ting Liu ◽  
Ying Mo ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Podocyte Injury

Differentiation of glomerular filter and tubular reabsorption apparatus during foetal development of the rat kidney

Development ◽  
1980 ◽  
Vol 58 (1) ◽  
pp. 157-175
Author(s):  
Jean Schaeverbeke ◽  
Madeleine Cheignon
Keyword(s):  
Molecular Weight ◽  
Basement Membrane ◽  
Proximal Tubule ◽  
High Molecular Weight ◽  
Glomerular Basement Membrane ◽  
Rat Kidney ◽  
Tubular Reabsorption ◽  
Foetal Development ◽  
Endocytic Vesicles ◽  
Glomerular Barrier

Differentiation of the glomerulus and the proximal tubule was studied in the rat foetus, especially with regard to the development of the protein filtration-reabsorption apparatus. Filtration starts several days before full differentiation of the glomerulus, when the glomerular basement membrane consists of a thin lamina alongside the podocyte membrane. Endocytosis is functional from this time, but fusion between endocytic vesicles and lysosome-like bodies occurs 2 days later. Foetal urine electrophoresis shows the presence of many proteins, including high molecular weight ones, this proteinuria seeming chiefly due to the immaturity of the glomerular barrier.

Synthesis of the glomerular basement membrane in the rat kidney

1976 ◽  
Vol 20 (1) ◽  
pp. 125-137
Author(s):  
W. Romen ◽  
B. Schultze ◽  
K. Hempel
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Rat Kidney

scholarly journals Acute podocyte injury is not a stimulus for podocytes to migrate along the glomerular basement membrane in zebrafish larvae

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Florian Siegerist ◽  
Antje Blumenthal ◽  
Weibin Zhou ◽  
Karlhans Endlich ◽  
Nicole Endlich
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Podocyte Injury ◽  
Zebrafish Larvae

Genetic inactivation of the laminin α5chain receptor Lu/BCAM leads to kidney and intestinal abnormalities in the mouse

2008 ◽  
Vol 294 (2) ◽  
pp. F393-F406 ◽  
Author(s):  
Cécile Rahuel ◽  
Anne Filipe ◽  
Léa Ritie ◽  
Wassim El Nemer ◽  
Natacha Patey-Mariaud ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Basement Membrane ◽  
Red Blood Cells ◽  
Glomerular Basement Membrane ◽  
Blood Cells ◽  
Laminin Receptor ◽  
Limited Information ◽  
Wild Type ◽  
Muscle Coat

Lutheran blood group and basal cell adhesion molecule (Lu/BCAM) has been recognized as a unique receptor for laminin α5chain in human red blood cells and as a coreceptor in epithelial, endothelial, and smooth muscle cells. Because limited information is available regarding the function of this adhesion glycoprotein in vivo, we generated Lu/BCAM-null mice and looked for abnormalities in red blood cells as well as in kidney and intestine, two tissues showing alteration in laminin α5chain-deficient mice. We first showed that, in contrast to humans, wild-type murine red blood cells failed to express Lu/BCAM. Lu/BCAM-null mice were healthy and developed normally. However, although no alteration of the renal function was evidenced, up to 90% of the glomeruli from mutant kidneys exhibited abnormalities characterized by a reduced number of visible capillary lumens and irregular thickening of the glomerular basement membrane. Similarly, intestine analysis of mutant mice revealed smooth muscle coat thickening and disorganization. Because glomerular basement membrane and smooth muscle coat express laminin α5chain and are in contact with cell types expressing Lu/BCAM in wild-type mice, these results provide evidence that Lu/BCAM, as a laminin receptor, is involved in vivo in the maintenance of normal basement membrane organization in the kidney and intestine.

Electron Microscopy of the Glomerular Basement Membrane of the Rat Kidney

2015 ◽  
pp. 45-53
Author(s):  
K. Oshima ◽  
M. Hatano ◽  
Y. Maeyama ◽  
N. Sugino ◽  
T. Takeuchi
Keyword(s):  
Electron Microscopy ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Rat Kidney
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