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

Citation
Cji. Raats et al., Expression of agrin, dystroglycan, and utrophin in normal renal tissue andin experimental glomerulopathies, AM J PATH, 156(5), 2000, pp. 1749-1765
Citations number
79
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
0002-9440 → ACNP
Volume
156
Issue
5
Year of publication
2000
Pages
1749 - 1765
Database
ISI
SICI code
0002-9440(200005)156:5<1749:EOADAU>2.0.ZU;2-L
Abstract
The dystrophin-glycoprotein complex, which comprises alpha- and beta-dystro glycan, sarcoglycans, and utrophin/dystrophin, links the cytoskeleton to ag rin and laminin in the basal lamina in muscle and epithelial cells. Recentl y, agrin was identified as a major heparan sulfate proteoglycan in the glom erular basement membrane. In the present study, we found mRNA expression fo r agrin, dystroglycan, and utrophin in kidney cortex, isolated glomeruli, a nd cultured podocytes and mesangial cells. In immunofluorescence, agrin was found in the glomerular basement membrane. The antibodies against alpha- a nd beta-dystroglycan and utrophin revealed a granular podocyte-like stainin g pattern along the glomerular capillary wall. With immunoelectron microsco py, agrin was found in the glomerular basement membrane, dystroglycan was d iffusely found over the entire cell surface of the podocytes, and utrophin was localized in the cytoplasm of the podocyte foot processes. In adriamyci n nephropathy, a decrease in the glomerular capillary wall staining for dys troglycan was observed probably secondary to the extensive fusion of foot p rocesses. 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 proce sses. In passive Heymann nephritis we observed no changes in the staining i ntensity and distribution of the dystrophin-glycoprotein complex by immunof luorescence and immunoelectron microscopy. From these data, we conclude tha t agrin, dystroglycan, and utrophin are present in the glomerular capillary wall and their ultrastructural localization supports the concept that thes e molecules are involved in linking the podocyte cytoskeleton to the glomer ular basement membrane.