Podocyte flattening and disorder of glomerular basement membrane are associated with splitting of dystroglycan-matrix interaction
| Autor: | Helga Poczewski, Agnes Davidovits, Brigitte Langer, Shunya Uchida, Katalyn Nagy-Bojarski, Kenichiro Kojima, Roland Sedivy, Dontscho Kerjaschki, Anny Hovorka |
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| Rok vydání: | 2004 |
| Předmět: |
musculoskeletal diseases
animal structures Kidney Glomerulus Lamina Rara Externa In Vitro Techniques Puromycin Aminonucleoside Basement Membrane Podocyte Rats Sprague-Dawley Necrosis Laminin Dystroglycan medicine Cell Adhesion Animals Protamines Dystroglycans Basement membrane Agrin Antibiotics Antineoplastic Membrane Glycoproteins biology Glomerular basement membrane Heparin Antagonists General Medicine Endocytosis Cell biology Dystroglycan complex Extracellular Matrix Rats Cytoskeletal Proteins Microscopy Electron medicine.anatomical_structure Nephrology Immunology biology.protein Female |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 15(8) |
| ISSN: | 1046-6673 |
| Popis: | The transmembrane component of the dystroglycan complex, a heterodimer of alpha- and beta-dystroglycan, was recently localized at the basal cell membrane domain of podocytes, and it was speculated that it serves as a device of the podocyte for maintaining the complex podocyte foot process architecture, and for regulating the exact position of its ligands, the matrix proteins laminin and agrin, in the glomerular basement membrane (GBM). The redistribution of dystroglycan in two experimental rat models of foot process flattening and proteinuria-i.e., podocyte damage induced by polycationic protamine sulfate perfusion, and reactive oxygen species (ROS)-associated puromycin aminonucleoside nephrosis-was examined. In both experimental diseases, aggregation and reduced density of alpha-dystroglycan by endocytosis by podocytes was observed. In in vitro solid-phase binding assays, protamine and ROS competed with the binding of alpha-dystroglycan with purified laminin and a recombinant C-terminal fragment of agrin that contains the dystroglycan-binding domain. These changes were associated with disorder of the fibrillar components of the lamina rara externa of the GBM, as confirmed quantitatively by fractal analysis. These results indicate that both polycation and ROS induce similar changes in the distribution of podocyte alpha-dystroglycan that involve competitive disruption of alpha-dystroglycan/matrix protein complexes, endocytosis of the liberated receptor by podocytes, and disorganization of the matrix protein arrangement in the lamina rara externa. This links functional damage of the dystroglycan complex with structural changes in the GBM. |
| Databáze: | OpenAIRE |
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