Role of Proteoglycans in Glomerular Function and Pathology

Farquhar, Marilyn G.; Lemkin, Margaret C.; Stow, Jennifer L.

doi:10.1007/978-1-4612-5284-9_54

Cited by 21 publications

(21 citation statements)

References 40 publications

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“…The presence of immunodetectable HSPG in the visceral epithelium together with our autoradiographic findings (29) suggest that these cells play the predominant role in the synthesis of basement membrane HSPG.…”

Section: Discussionsupporting

confidence: 68%

“…That the proteoglycans recognized were (14). We conclude (29) (26) of this approach for localizing antigens within the layers of the GBM. We believe that the more consistent, restricted localization of HSPG to the laminae rarae obtained by the direct immunoperoxidase and frozen thin-section techniques more accurately reflects the sites where the core proteins are concentrated; moreover, it corresponds to the site of localization of the heparan sulfate side chains as detected with cationic probes (3,8).…”

Section: Discussionmentioning

confidence: 78%

“…By contrast, in preparations incubated with an antibody raised against liver cell membrane HSPG (28) and stained by indirect immunoperoxidase, diaminobenzidine-HCl reaction product was found on the surfaces of glomerular epithelial and endothelial cells and on the basolateral membranes of tubule epithelia (14,29), but no reaction product was detected in the GBM or in other renal basement membranes.…”

Section: When [ I S]methionine-labeled Fractions Were Analyzed Bymentioning

confidence: 93%

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Basement membrane heparan sulfate proteoglycans are concentrated in the laminae rarae and in podocytes of the rat renal glomerulus.

Stow¹,

Sawada²,

Farquhar³

1985

Proc. Natl. Acad. Sci. U.S.A.

141

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A polyclonal antibody was raised against a proteoglycan fraction purified from extracts of isolated rat renal glomeruli. The antibody was characterized by column chromatography and by NaDodSO4/PAGE analysis of immunoprecipitates and was shown to recognize specifically the core protein of a population of heparan sulfate proteoglycans (Mr 130,000) found in the glomerular basement membrane and in other renal basement membranes. The antibody was used to localize the core proteins of this population of heparan sulfate proteoglycans (HSPG) in the glomerulus by immunoelectron microscopic techniques. These HSPG were found to be concentrated in the lamina rarae interna and externa of the glomerular basement membrane (GBM) and precursor forms were detected in the endoplasmic reticulum and Golgi cisternae of glomerular visceral epithelial cells (podocytes).Heparan sulfate proteoglycans (HSPG) are now recognized to be widely distributed if not ubiquitous components of basement membranes (basal laminae) (1, 2). They were originally discovered in the glomerular basement membrane (GBM) (3, 4), where they represent important structural components required for the maintenance of its selective permeability properties (5, 6). Previous work from this laboratory (7) established that HSPG isolated from the rat GBM are relatively small (mean Mr 130,000) and possess approximately four heparan sulfate side chains (Mr 26,000). By cytochemical techniques the heparan sulfate side chains of the HSPG were found to be concentrated in regularly spaced 60-nm anionic sites in the inner and outermost layers (lamina rara interna and externa) of the GBM (3,8). The location of the core protein of these HSPG has not been resolved because to date no specific antibodies have been generated against HSPG from the GBM, and immunocytochemical studies utilizing antibodies raised against HSPG derived from other basement membrane sources have provided conflicting evidence on the localization of HSPG in the GBM (9, 10). HSPG from various sources, including different sources of basement membranes (11)(12)(13) (totaling 5 mCi) in 120-g rats over a 12-hr period (15).Isolation of Glomerular Proteoglycans. Glomeruli were isolated from the radiolabeled kidneys (7) and extracted in 10 vol of 4 M guanidine HCI (pH 6.0) containing 0.5% Chaps and protease inhibitors (1 mM PMSF/10 mM N-ethylmaleimide/10 mM EDTA/10 mM 6-aminohexanoic acid/5 mM benzamidine-HCI) for 16 hr at 4°C with shaking. The unextracted residue was pelleted by centrifugation (1000 x g for 10 min) and proteoglycans were purified according to Yanagishita and Hascall (16) by passing the clarified extract over a Sephadex G-50 column, elution with 8 M urea/50 mM sodium acetate/0.15 M NaCl, pH 6, followed by application of the excluded volume onto a DEAE-Sephacel column and elution with a continuous NaCl gradient (0. 15-1.5 M). Fractions corresponding to the peaks of radioactivity that eluted in the starting buffer (peak 1) and at 0.45-1.0 M NaCl (peak 2) were collected, dialyzed overnight aga...

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 78%

Section: When [ I S]methionine-labeled Fractions Were Analyzed Bymentioning

confidence: 93%

See 1 more Smart Citation

Basement membrane heparan sulfate proteoglycans are concentrated in the laminae rarae and in podocytes of the rat renal glomerulus.

Stow¹,

Sawada²,

Farquhar³

1985

Proc. Natl. Acad. Sci. U.S.A.

141

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“…In the kidney, HS is the major acid glycosaminoglycans (GAGs) constituent of both the glomerular and tubular basement membranes (GBM and TBM) [19]. Basement membrane type HSPG in GBM, so called perlecan is important for maintaining the integrity of glomerular size and the charge barrier [20,21]. A decrease in negatively charged molecules within the GBM is thought to be responsible for the albuminuria that arises under various nephropathic conditions [19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

“…Basement membrane type HSPG in GBM, so called perlecan is important for maintaining the integrity of glomerular size and the charge barrier [20,21]. A decrease in negatively charged molecules within the GBM is thought to be responsible for the albuminuria that arises under various nephropathic conditions [19][20][21][22]. On the other hand, the function of other type of HSPG, such as syndecan [23,24], remains unclear in the kidney.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Heparan Sulfate Proteoglycan on the Cultured Renal Epithelial Cells during Oxalate Exposure

Matsuo

2008

Kurume Med. J.

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Biosynthesis and Structure of the Basement Membrane Proteoglycan Containing Heparan Sulphate Side‐Chains

Hassell

Noonan

Ledbetter

et al. 2007

Novartis Foundation Symposia

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Role of Proteoglycans in Glomerular Function and Pathology

Cited by 21 publications

References 40 publications

Basement membrane heparan sulfate proteoglycans are concentrated in the laminae rarae and in podocytes of the rat renal glomerulus.

Basement membrane heparan sulfate proteoglycans are concentrated in the laminae rarae and in podocytes of the rat renal glomerulus.

Increased Expression of Heparan Sulfate Proteoglycan on the Cultured Renal Epithelial Cells during Oxalate Exposure

Biosynthesis and Structure of the Basement Membrane Proteoglycan Containing Heparan Sulphate Side‐Chains

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