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PMID: 10793086 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of agrin, dystroglycan, and utrophin in normal renal tissue and in experimental glomerulopathies.

The American journal of pathology ·Vol. 156 ·No. 5 ·2000-05-00 ·Pages 1749-65

Raats CJ, van den Born J, Bakker MA, Oppers-Walgreen B, Pisa BJ, Dijkman HB, Assmann KJ, Berden JH

Abstract

The dystrophin-glycoprotein complex, which comprises alpha- and beta-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 alpha- and beta-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.

MeSH Terms
Agrin/analysis,genetics Animals Cytoskeletal Proteins/analysis,genetics Doxorubicin/administration & dosage,adverse effects Dystroglycans Gene Expression Glomerular Mesangium/cytology,metabolism,ultrastructure Glomerulonephritis/genetics,metabolism,pathology Immunohistochemistry Kidney/cytology,metabolism,ultrastructure Kidney Cortex/chemistry,metabolism,ultrastructure Kidney Glomerulus/cytology,metabolism,ultrastructure Male Membrane Glycoproteins/analysis,genetics Membrane Proteins/analysis,genetics Microscopy, Immunoelectron Nephrotic Syndrome/chemically induced,genetics,pathology RNA, Messenger/genetics,metabolism Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Utrophin
Chemicals
Agrin Cytoskeletal Proteins Membrane Glycoproteins Membrane Proteins RNA, Messenger Utrophin Dystroglycans Doxorubicin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Raats C J
Division of Nephrology and Department of Pathology, University Hospital St. Radboud, Nijmegen, The Netherlands.
van den Born J
Bakker M A
Oppers-Walgreen B
Pisa B J
Dijkman H B
Assmann K J
Berden J H
References (78)
78 references, click to expand
  1. Distribution of dystrophin isoforms and dystrophin-associated proteins 43DAG (A3a) and 50DAG (A2) in various monkey tissues.
    J Biochem. 1993 Dec;114(6):936-41 PMID: 8138555
  2. Identification and purification of an agrin receptor from Torpedo postsynaptic membranes: a heteromeric complex related to the dystroglycans.
    Neuron. 1994 May;12(5):1173-80 PMID: 8185951
  3. Relationship of a dystrophin-associated glycoprotein to junctional acetylcholine receptor clusters in rat skeletal muscle.
    Neuromuscul Disord. 1993 Sep-Nov;3(5-6):503-6 PMID: 8186701
  4. Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor.
    Cell. 1994 Jun 3;77(5):675-86 PMID: 8205617
  5. Structural domains of agrin required for clustering of nicotinic acetylcholine receptors.
    EMBO J. 1994 Jun 15;13(12):2814-21 PMID: 8026466
  6. GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit.
    J Biol Chem. 1994 Aug 5;269(31):19953-62 PMID: 7519601
  7. Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses.
    Nat Genet. 1999 Nov;23(3):338-42 PMID: 10610181
  8. Focal glomerular sclerosis in nephrotic patients: an electron microscopic study of glomerular podocytes.
    Kidney Int. 1975 Feb;7(2):111-22 PMID: 1113452
  9. Relationship between proteinuria and epithelial cell changes in minimal lesion glomerulopathy.
    Nephron. 1976;16(4):310-7 PMID: 765875
  10. Epithelial foot-process effacement in patients with proteinuria.
    Am J Clin Pathol. 1979 Oct;72(4):529-32 PMID: 495558
  11. Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events.
    Lab Invest. 1982 Jan;46(1):16-23 PMID: 6172662
  12. Foot process fusion and glomerular filtration rate in minimal change nephrotic syndrome.
    Kidney Int. 1984 Apr;25(4):696-700 PMID: 6482174
  13. Identification of a major sialoprotein in the glycocalyx of human visceral glomerular epithelial cells.
    J Clin Invest. 1986 Nov;78(5):1142-9 PMID: 3533998
  14. Epithelial polyanion (podocalyxin) is found on the sides but not the soles of the foot processes of the glomerular epithelium.
    Am J Pathol. 1986 Nov;125(2):309-18 PMID: 3538890
  15. Agrin is a heparan sulfate proteoglycan.
    J Biol Chem. 1995 Feb 17;270(7):3392-9 PMID: 7852425
  16. Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage.
    Cell. 1995 Mar 10;80(5):675-9 PMID: 7889563
  17. Direct podocyte damage in the single nephron leads to albuminuria in vivo.
    Kidney Int. 1995 Apr;47(4):1078-86 PMID: 7783404
  18. Non-muscle alpha-dystroglycan is involved in epithelial development.
    J Cell Biol. 1995 Jul;130(1):79-91 PMID: 7790379
  19. Molecular cloning of cDNAs encoding human GLEPP1, a membrane protein tyrosine phosphatase: characterization of the GLEPP1 protein distribution in human kidney and assignment of the GLEPP1 gene to human chromosome 12p12-p13.
    Genomics. 1995 May 1;27(1):174-81 PMID: 7665166
  20. Comparative expressed-sequence-tag analysis of differential gene expression profiles in PC-12 cells before and after nerve growth factor treatment.
    Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8303-7 PMID: 7667285
  21. Muscular dystrophies: diseases of the dystrophin-glycoprotein complex.
    Science. 1995 Nov 3;270(5237):755-6 PMID: 7481760
  22. Ultrastructural localization of adhalin in normal murine skeletal myofiber.
    Ann Neurol. 1996 Feb;39(2):217-23 PMID: 8967753
  23. In vivo enzymatic removal of alpha 2-->6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury.
    Lab Invest. 1996 May;74(5):907-20 PMID: 8642786
  24. Localization of the dystrophin binding site at the carboxyl terminus of beta-dystroglycan.
    Biochem Biophys Res Commun. 1996 Jun 14;223(2):272-7 PMID: 8670271
  25. Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell membrane.
    J Biol Chem. 1996 Sep 20;271(38):23418-23 PMID: 8798547
  26. Re-evaluation of foot process effacement in acute puromycin aminonucleoside nephrosis.
    Kidney Int. 1996 Oct;50(4):1278-87 PMID: 8887289
  27. Dystroglycan: an extracellular matrix receptor linked to the cytoskeleton.
    Curr Opin Cell Biol. 1996 Oct;8(5):625-31 PMID: 8939660
  28. Electron microscopic observations of triple immunogold labelling for dystrophin, beta-dystroglycan and adhalin in human skeletal myofibers.
    Acta Neuropathol. 1996 Dec;92(6):569-75 PMID: 8960314
  29. Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis.
    Am J Pathol. 1987 Feb;126(2):220-9 PMID: 3826295
  30. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  31. An evaluation of the development of experimental membranous nephropathy.
    Kidney Int. 1987 Jun;31(6):1267-78 PMID: 3613404
  32. Acetylcholine receptor-aggregating proteins are associated with the extracellular matrix of many tissues in Torpedo.
    J Cell Biol. 1988 Apr;106(4):1263-72 PMID: 2834403
  33. Massive proteinuria induced in rats by a single intravenous injection of a monoclonal antibody.
    J Immunol. 1988 Aug 1;141(3):807-14 PMID: 3397534
  34. A beta 1-integrin receptor for fibronectin in human kidney glomeruli.
    Am J Pathol. 1989 Feb;134(2):481-9 PMID: 2521774
  35. Glomerular epithelial detachment, not reduced charge density, correlates with proteinuria in adriamycin and puromycin nephrosis.
    Lab Invest. 1989 Dec;61(6):650-60 PMID: 2601299
  36. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle.
    Nature. 1990 May 24;345(6273):315-9 PMID: 2188135
  37. Identification of a chromosome 6-encoded dystrophin-related protein.
    J Biol Chem. 1990 Oct 5;265(28):16717-20 PMID: 2170350
  38. Binding of monoclonal antibodies to glomerular endothelium, slit membranes, and epithelium after in vivo injection. Localization of antigens and bound IgGs by immunoelectron microscopy.
    Am J Pathol. 1990 Oct;137(4):913-27 PMID: 1977320
  39. Monoclonal antibodies against membrane proteins of the rat glomerulus. Immunochemical specificity and immunofluorescence distribution of the antigens.
    Am J Pathol. 1990 Oct;137(4):929-44 PMID: 1699424
  40. Glycoprotein complex anchoring dystrophin to sarcolemma.
    J Biochem. 1990 Nov;108(5):748-52 PMID: 2081733
  41. Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3243-7 PMID: 2014247
  42. Structure and expression of a rat agrin.
    Neuron. 1991 May;6(5):811-23 PMID: 1851019
  43. Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein.
    J Histochem Cytochem. 1991 Aug;39(8):1047-56 PMID: 1856454
  44. Membrane organization of the dystrophin-glycoprotein complex.
    Cell. 1991 Sep 20;66(6):1121-31 PMID: 1913804
  45. Current status of the structural and functional basis of glomerular filtration and proteinuria.
    Semin Nephrol. 1991 Jul;11(4):390-413 PMID: 1947494
  46. Rat glomerular cells do not express podocytic markers when cultured in vitro.
    Lab Invest. 1991 Nov;65(5):548-57 PMID: 1753704
  47. Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines.
    J Cell Biol. 1991 Dec;115(6):1695-700 PMID: 1757469
  48. Quantitative studies of monoclonal antibody 5-1-6-induced proteinuric state in rats.
    Clin Exp Immunol. 1992 Feb;87(2):215-9 PMID: 1735184
  49. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix.
    Nature. 1992 Feb 20;355(6362):696-702 PMID: 1741056
  50. Expression of the N-terminal domain of dystrophin in E. coli and demonstration of binding to F-actin.
    FEBS Lett. 1992 Apr 27;301(3):243-5 PMID: 1577159
  51. A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats.
    Kidney Int. 1992 Jan;41(1):115-23 PMID: 1593846
  52. Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells.
    Kidney Int. 1992 Jan;41(1):124-31 PMID: 1593847
  53. Dystrophin or a "related protein" in Duchenne muscular dystrophy?
    Acta Neurol Scand. 1992 Jul;86(1):8-14 PMID: 1519480
  54. Structure and chromosomal localization of the mammalian agrin gene.
    J Neurosci. 1992 Sep;12(9):3535-44 PMID: 1326608
  55. Cloning and expression of full length mouse utrophin: the differential association of utrophin and dystrophin with AChR clusters.
    FEBS Lett. 1996 Dec 2;398(2-3):259-64 PMID: 8977119
  56. Antiproteinuric effect of ciclosporin A in adriamycin nephropathy in rats.
    Nephron. 1997;75(3):336-41 PMID: 9069457
  57. A role of dystroglycan in schwannoma cell adhesion to laminin.
    J Biol Chem. 1997 May 23;272(21):13904-10 PMID: 9153251
  58. Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice.
    Hum Mol Genet. 1997 Jun;6(6):831-41 PMID: 9175728
  59. Induction of differentiation in cultured rat and human podocytes.
    J Am Soc Nephrol. 1997 May;8(5):697-705 PMID: 9176839
  60. Laminin-alpha2 but not -alpha1-mediated adhesion of human (Duchenne) and murine (mdx) dystrophic myotubes is seriously defective.
    FEBS Lett. 1997 May 26;408(3):341-4 PMID: 9188790
  61. Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis.
    Am J Pathol. 1997 Oct;151(4):1141-52 PMID: 9327748
  62. Hydroxyl radicals depolymerize glomerular heparan sulfate in vitro and in experimental nephrotic syndrome.
    J Biol Chem. 1997 Oct 17;272(42):26734-41 PMID: 9334259
  63. Integrins mediate adhesion to agrin and modulate agrin signaling.
    Development. 1997 Oct;124(19):3909-17 PMID: 9367446
  64. Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue.
    J Biol Chem. 1998 Jan 2;273(1):600-5 PMID: 9417121
  65. Bidirectional signaling between sarcoglycans and the integrin adhesion system in cultured L6 myocytes.
    J Biol Chem. 1998 Jan 16;273(3):1583-90 PMID: 9430699
  66. Distribution of dystroglycan in normal adult mouse tissues.
    J Histochem Cytochem. 1998 Apr;46(4):449-57 PMID: 9524190
  67. Differential expression of agrin in renal basement membranes as revealed by domain-specific antibodies.
    J Biol Chem. 1998 Jul 10;273(28):17832-8 PMID: 9651386
  68. Co-localization of dystrophin and beta-dystroglycan demonstrated in en face view by double immunogold labeling of freeze-fractured skeletal muscle.
    J Histochem Cytochem. 1998 Aug;46(8):945-54 PMID: 9671444
  69. Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane.
    Nephrol Dial Transplant. 1999 Sep;14(9):2119-29 PMID: 10489220
  70. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane.
    J Histochem Cytochem. 1998 Jan;46(1):19-27 PMID: 9405491
  71. Different distributions of dystrophin and related proteins at nerve-muscle junctions.
    Neuroreport. 1992 Oct;3(10):857-60 PMID: 1421088
  72. Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane-associated in cultured cell lines.
    FEBS Lett. 1992 Nov 16;313(1):19-22 PMID: 1426262
  73. Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle.
    Nature. 1992 Dec 10;360(6404):588-91 PMID: 1461282
  74. Primary structure of dystrophin-related protein.
    Nature. 1992 Dec 10;360(6404):591-3 PMID: 1461283
  75. A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin.
    J Cell Biol. 1993 Aug;122(4):809-23 PMID: 8349731
  76. Developmental regulation of highly active alternatively spliced forms of agrin.
    Neuron. 1993 Sep;11(3):479-90 PMID: 8398141
  77. Primary structure and muscle-specific expression of the 50-kDa dystrophin-associated glycoprotein (adhalin).
    J Biol Chem. 1993 Nov 15;268(32):23739-42 PMID: 8226900
  78. Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin.
    Eur J Biochem. 1994 Mar 1;220(2):283-92 PMID: 8125086
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65046-8
Published
2000-05-00
Pages
1749-65
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1876919
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65046-8 PMC Full Text View journal details
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