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

Am J Pathol. 2000 May;156(5):1749-65. doi: 10.1016/S0002-9440(10)65046-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrin / analysis
  • Agrin / genetics*
  • Animals
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics*
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Dystroglycans
  • Gene Expression
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / metabolism
  • Glomerular Mesangium / ultrastructure
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / metabolism
  • Glomerulonephritis / pathology
  • Immunohistochemistry
  • Kidney / cytology
  • Kidney / metabolism*
  • Kidney / ultrastructure
  • Kidney Cortex / chemistry
  • Kidney Cortex / metabolism
  • Kidney Cortex / ultrastructure
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / ultrastructure
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics*
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Microscopy, Immunoelectron
  • Nephrotic Syndrome / chemically induced
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Utrophin

Substances

  • Agrin
  • Cytoskeletal Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • Utrophin
  • Dystroglycans
  • Doxorubicin