Pores in the Glomerular Basement Membrane Revealed by Ultrahigh- Resolution Scanning Electron Microscopy

Hironaka, Kazue; Makino, Hírofumi; Yamasaki, Yasushi; Ota, Zensuke

doi:10.1159/000187418

Cited by 19 publications

(14 citation statements)

References 7 publications

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“…7], and this structure was subsequently confirmed by various methods [9][10][11]. We have recently confirmed the meshwork structure of G B M [21,22,24] as well as tubular basement 593 membrane. Bowman's capsule basement membrane and peritubular capillary basement membrane [22] by high-res olution scanning electron microscopy which has a resolving power o f 0.5 nm.…”

Section: Discussionsupporting

confidence: 58%

“…Morphometrically, the inner surfaces o f the EVA1 membranes were very similar to G B M in vivo with pores o f 10 nm in diameter by high-resolution scanning electron microscopy [22,24]. The basic difference in the structure o f the EVAI membrane from G B M is its unsymmetrical structure; the inner surface is porous in contrast to the fibrous outer surface.…”

Section: Discussionmentioning

confidence: 94%

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Study of Glomerular Permselectivity for Proteins of the Glomerular Basement Membrane Using a Dialyzer Model

Nagake¹,

Makino²,

Hironaka³

et al. 1993

Nephron

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The glomerular basement membrane (GBM) is considered to regulate glomerular permselectivity for proteins by acting as both size barrier and charge barrier. Since heparan sulfate-proteoglycan (HS-PG), which forms the charge barrier of GBM, contains a sulfonic acid, we made membranes with various degrees of negative charge models of GBM by addition of sulfonic acid to ethylene vinyl alcohol (EVAL) membranes. A high-resolution scanning electron-microscopic study revealed no ultrastructural alterations after adding sulfonic acid to EVAL membranes. Both neutrally and negatively charged membranes had porous structures in the inner surface of the membranes. The interrelation between the two actions of size and charge of GBM was studied using special dialyzers with various degrees of negative charge and different pore sizes. The negatively charged membranes adsorbed proteins with positive charge and repulsed proteins with negative charge. The degrees of adsorption and repulsion were weaker in membranes with larger pores and were stronger for proteins with larger molecular weights. The permselectivity for proteins of a charged membrane depends largely upon the interrelation between the pore size of the membrane and the size of the proteins. It is, therefore, suggested that the presence of a size barrier in GBM is necessary for the charge barrier to effectively exert glomerular permselectivity for proteins. Our study may lead to the development of a dialyzer with higher permselectivity by adding sulfonic acid rather than conventional dialyzers.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 94%

Study of Glomerular Permselectivity for Proteins of the Glomerular Basement Membrane Using a Dialyzer Model

Nagake¹,

Makino²,

Hironaka³

et al. 1993

Nephron

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“…However, glycoproteins that cover the endothelial fenestrae may exert steric hindrance to the macromolecules pas- sage. More importantly, the openings of the glomerular basement membrane protein mesh seem to have variable dimension (from 10 to 20 nm in radius), 31,32 and this structure is expected to contribute, at least in part, to the sieving properties of the capillary membrane, even if experimental evidence suggests that the contribution of the glomerular basement membrane alone on glomerular membrane permeability to macromolecules is less than that of the cellular components (both endothelial and epithelial layer). 33 Thus, the overall sieving coefficient of the glomerular membrane is expected to result from the contribution of these three layers in series, as described in details by Deen and Lazzara.…”

Section: Discussionmentioning

confidence: 99%

Imaging of the Porous Ultrastructure of the Glomerular Epithelial Filtration Slit

Gagliardini

Conti

Benigni

et al. 2010

Journal of the American Society of Nephrology

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The ultrastructure of the glomerular filtration slit is still controversial. In the last 30 years, observations from transmission electron microscopy (TEM) and theoretical analysis of solute clearance produced conflicting results. Here, we used scanning EM with a high-sensitivity detector to image the deepest regions of the filtration slits and report a previously undescribed organization of the slits' ultrastructure. In contrast to previous TEM imaging, we observed circular and ellipsoidal pores in the podocyte junctions mainly located in the central region of the slit diaphragm. The normal mean pore radius estimated by digital morphometric analysis had a log-normal distribution, with an average value of 12.1 nm. In proteinuric pathologic conditions, the mean pore radius values were also log-normally distributed with the presence of some very large pores, exceeding the sizes observed in normal conditions. Our morphologic analysis suggests that the filtration slit is a heteroporous structure instead of the previously proposed zipper-like structure. Selective changes in the ultrastructural organization of the pores may be responsible for the increased filtration of plasma proteins in glomerular disease. The permeability properties of the glomerular capillary wall allow the filtration of high water flow and small solutes but efficient retention of plasma proteins the size of albumin or larger. 1 It has been indicated that most of the restriction of macromolecule ultrafiltration is caused by the epithelial filtration slits, because plasma proteins can cross endothelial cells and glomerular basement membrane (GBM) more easily. 2 Changes in glomerular permselective function resulting in increased glomerular filtration of plasma proteins and incomplete tubular reabsorption are responsible for loss of proteins in the urine. These events have been linked to the progression of renal diseases. 3 With the aim to characterize the mechanisms behind proteinuria, in the last 30 years, solute clearance techniques have been used to estimate the selective properties of the glomerular barrier in experimental models of nephropathy and in patients. In particular, glomerular size-selective function has been studied using renal clearance of neutral test macromolecules (i.e., neutral dextran and Ficoll) that are not secreted or reabsorbed at the tubular level. Theoretical models of glomerular size selectivity have been conventionally used to derive intrinsic membrane selective properties from fractional clearance of test macromolecules in terms of density and size of hypothetical pores perforating the glomerular capillary wall. 2,4,5 Thus, according to the two-pore

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“…In the present study, we observed a fine meshwork structure in proximal and distal TBM and in the GBM, supporting the proposition that a polygonal meshwork structure is a common basic ultrastructural feature of various basement membranes. However, the size of the pores in these meshwork structures differed by site within the nephron [10,17,18]. These dissimilarities among renal basement membranes reasonably might reflect differences in distribution and relative amount of major basement membrane components such as type IV collagen, laminin, HS-PG, fibronectin, and other glycoproteins such as entactin [17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Ultrastructural Comparison of Renal Glomerular and Tubular Basement Membranes

Ogawa¹,

Ota²,

Shikata³

et al. 1999

Am J Nephrol

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Background/Aims: Glomerular basement membranes (GBM) and tubular basement membranes (TBM) consist of a fine meshwork composed mainly of type IV collagen. Each segment of tubules has specialized physiologic functions, and thus we investigated the ultrastructure of various basement membranes in rat kidneys. Methods: Since purifying basement membranes from different tubule segments is technically challenging, we employed tissue negative staining rather than conventional negative staining to compare the ultrastructures of proximal and distal TBM and GBM in normal rats. We also assessed the distribution of extracellular matrix components including type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin in the basement membranes by immunohistochemistry. Results: TBM and GBM of normal rats showed a fine meshwork structure consisting of fibrils forming small round to oval pores. Short- and long-pore diameters in proximal tubules were 3.3 ± 0.5 and 3.9 ± 0.6 nm, respectively, and in distal tubules 3.5 ± 0.7 and 4.3 ± 0.8 nm, respectively. For GBM the respective diameters were 2.5 ± 0.5 and 3.0 ± 0.5 nm. Immunohistochemical analysis showed no significant difference in distribution of extracellular matrix components between proximal and distal TBM. However, immunofluorescence scores of α1 chain of type IV collagen, fibronectin, and laminin were higher in the TBM than in the GBM. On the other hand, heparan sulfate proteoglycan was higher in the GBM. Conclusion: Ultrastructural differences in renal basement membranes may be related to differences in physiologic function in each segment.

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Pores in the Glomerular Basement Membrane Revealed by Ultrahigh- Resolution Scanning Electron Microscopy

Cited by 19 publications

References 7 publications

Study of Glomerular Permselectivity for Proteins of the Glomerular Basement Membrane Using a Dialyzer Model

Study of Glomerular Permselectivity for Proteins of the Glomerular Basement Membrane Using a Dialyzer Model

Imaging of the Porous Ultrastructure of the Glomerular Epithelial Filtration Slit

High-Resolution Ultrastructural Comparison of Renal Glomerular and Tubular Basement Membranes

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