Differential Expression of Agrin in Renal Basement Membranes As Revealed by Domain-specific Antibodies

Raats, C.J.I.; Bakker, Marinka A.H.; Hoch, Werner; Tamboer, W.P.M.; Groffen, Alexander J.; Heuvel, L.P.W.J. van den; Berden, Jo H. M.; Born, Jacob van den

doi:10.1074/jbc.273.28.17832

Cited by 76 publications

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“…1c). These results indicate that the decreased staining of the GBM by antiheparan sulphate antibody JM403 is not due to reduced synthesis of the core protein of agrin, which is the major heparan sulphate proteoglycan in the GBM [24,25]. In this analysis we also observed an inverse correlation between the heparan sulphate domain content of the GBM and the level of proteinuria (Fig.…”

Section: Resultssupporting

confidence: 66%

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

et al. 2007

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Aims/hypothesis Recent studies suggest that loss of heparan sulphate in the glomerular basement membrane (GBM) of the kidney with diabetic nephropathy is due to the increased production of heparanase, a heparan sulphate-degrading endoglycosidase. Our present study addresses whether heparan sulphate with different modifications is differentially reduced in the GBM and whether heparanase selectively cleaves heparan sulphate with different domain specificities. Methods The heparan sulphate content of renal biopsies (14 diabetic nephropathy, five normal) were analysed by immunofluorescence staining with four anti-heparan sulphate antibodies: JM403, a monoclonal antibody (mAb) recognising N-unsubstituted glucosamine residues; two phage displayderived single chain antibodies HS4C3 and EW3D10, defining sulphated heparan sulphate domains; and anti-K5 antibody, an mAb recognising unmodified heparan sulphate domains. Results We found that modified heparan sulphate domains (JM403, HS4C3 and EW3D10), but not unmodified domains (anti-K5) and agrin core protein were reduced in the GBM of kidneys from patients with diabetic nephropathy, compared with controls. Glomerular heparanase levels were increased in diabetic nephropathy kidneys and inversely correlated with the amounts of modified heparan sulphate domains. Increased heparanase production and loss of JM403 staining in the GBM Diabetologia (2008) 51:372-382

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Section: Resultssupporting

confidence: 66%

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

et al. 2007

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“…Most TBMs lacked staining for the C-terminus of agrin, whereas the N-terminus of agrin was present in most TBMs. 17 The difference in GBM staining pattern for N-and C-terminal agrin in the present study could be due to a reduced accessibility of the perimesangial GBM regions for the antibodies. This is, however, not very likely because the mAb against N-terminal agrin clearly stained both peripheral and perimesangial GBM parts.…”

Section: Discussionmentioning

confidence: 53%

“…54 Furthermore, agrin is a major heparan sulfate proteoglycan in the adult GBM. 17,55 The anionic heparan sulfate side chains of agrin play an important role in the maintenance of the charge-dependent permeability of the GBM. 56 -58 In the present study, we observed a difference in ultrastructural localization between the N-and C-terminus of agrin.…”

Section: Discussionmentioning

confidence: 99%

“…17 mAb MI-90 stains most tubular basement membranes (TBMs) in a linear fashion, but somewhat less intense than the GBM, whereas the TBMs are negative or weakly stained by mAb Agr-131. Bowman's capsule, basement membranes (BMs) of endothelial cells in peritubular capillaries, and smooth muscle cells of arteries and arterioles are negative for both mAbs (Figure 2, A and B).…”

Section: Expression Of Agrin Dystroglycan and Utrophin In Normal Kimentioning

confidence: 99%

“…Details on the used antibodies are given in Table 2. 17,[43][44][45][46][47][48] Primary antibodies were diluted in PBS containing 1% bovine serum albumin (BSA) and 0.05% sodium azide (IF-buffer), fluorescein isothiocyanate-labeled secondary antibodies were diluted in IF-buffer containing 10% normal rat serum (for IF on rat tissue), all antibodies were incubated during 45 minutes at room temperature. To evaluate the deposition of sheep and rat IgG and complement factor C3c in the GCW of rats with PHN, sections were directly incubated with fluorescein isothiocyanate-labeled rabbit anti-sheep IgG (Southern, Birmingham, AL) diluted 1:100 in IF-buffer, goat anti-rat IgG and goat anti-rat C3c (both from Nordic, Tilburg, The Netherlands) both diluted 1:50 in IF-buffer.…”

Section: Immunofluorescencementioning

confidence: 99%

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Expression of Agrin, Dystroglycan, and Utrophin in Normal Renal Tissue and in Experimental Glomerulopathies

Raats

Born

Bakker

et al. 2000

The American Journal of Pathology

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103

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The dystrophin-glycoprotein complex, which comprises ␣-and ␤-dystroglycan, sarcoglycans, and utrophin/dystrophin, links the cytoskeleton to agrin and laminin in the basal lamina in muscle and epithelial cells. Recently, agrin was identified as a major heparan sulfate proteoglycan in the glomerular basement membrane. In the present study, we found mRNA expression for agrin, dystroglycan, and utrophin in kidney cortex, isolated glomeruli, and cultured podocytes and mesangial cells. In immunofluorescence, agrin was found in the glomerular basement membrane. The antibodies against ␣-and ␤-dystroglycan and utrophin revealed a granular podocyte-like staining pattern along the glomerular capillary wall. With immunoelectron microscopy, agrin was found in the glomerular basement membrane, dystroglycan was diffusely found over the entire cell surface of the podocytes, and utrophin was localized in the cytoplasm of the podocyte foot processes. In adriamycin nephropathy, a decrease in the glomerular capillary wall staining for dystroglycan was observed probably secondary to the extensive fusion of foot processes. Immunoelectron microscopy showed a different distribution pattern as compared to the normal kidney, with segmentally enhanced expression of dystroglycan at the basal side of the extensively fused podocyte foot processes. In passive Heymann nephritis we observed no changes in the staining intensity and distribution of the dystrophin-glycoprotein complex by immunofluorescence and immunoelectron microscopy. From these data, we conclude that agrin, dystroglycan, and utrophin are present in the glomerular capillary wall and their ultrastructural localization supports the concept that these molecules are involved in linking the podocyte cytoskeleton to the glomerular basement membrane. (Am J Pathol 2000, 156:1749 -1765) Dystroglycan (DG) is an important member of the dystrophin-glycoprotein complex (DGC) which links the subsarcolemmal cytoskeleton to the basal lamina in skeletal muscle.1 The importance of this link becomes clear from the severe muscular dystrophies resulting from mutations in genes that encode different members of the DGC. 2-5

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Renal Tubular‐ and Vascular Basement Membranes and their Mimicry in Engineering Vascularized Kidney Tubules

Genderen

Jansen

Cheng

et al. 2018

Adv Healthcare Materials

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The high prevalence of chronic kidney disease leads to an increased need for renal replacement therapies. While there are simply not enough donor organs available for transplantation, there is a need to seek other therapeutic avenues as current dialysis modalities are insufficient. The field of regenerative medicine and whole organ engineering is emerging, and researchers are looking for innovative ways to create (part of) a functional new organ. To biofabricate a kidney or its functional units, it is necessary to understand and learn from physiology to be able to mimic the specific tissue properties. Herein is provided an overview of the knowledge on tubular and vascular basement membranes' biochemical components and biophysical properties, and the major differences between the two basement membranes are highlighted. Furthermore, an overview of current trends in membrane technology for developing renal replacement therapies and to stimulate kidney regeneration is provided.

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Differential Expression of Agrin in Renal Basement Membranes As Revealed by Domain-specific Antibodies

Cited by 76 publications

References 50 publications

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

Expression of Agrin, Dystroglycan, and Utrophin in Normal Renal Tissue and in Experimental Glomerulopathies

Renal Tubular‐ and Vascular Basement Membranes and their Mimicry in Engineering Vascularized Kidney Tubules

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