title: Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis.
abstract: Extensive flattening of podocyte foot processes and increased permeability of the glomerular capillary filter are the major pathologic features of minimal change nephrosis (MCN) and focal segmental glomerulosclerosis (FSGS). Adhesion proteins anchor and stabilize podocytes on the glomerular basement membrane (GBM), and presumably are involved in the pathogenesis of foot process flattening. Thus far, ao3 P,-integrin was localized to basal cell membrane domains. In this report, ao- and 3-dystroglycan (DG) were detected at precisely the sa-ne location by immunoelectron microscopy. and the presence of ac- and /-DG chains was confirmed by immunoblotting on isolated human glomeruli. Because the major DG binding partners in the GBM (laminin, agrin, perlecan), and the intracellular dystrophin analogue utrophin are also present in glomeruli, it appears that podocytes adhere to the GBM via DG complexes, similar to muscle fibers in which actin is linked via dystrophin and DG to the extracellular matrix. As with muscle cells, it is therefore plausible that podocytes use precisely actin-guided DG complexes at their "soles" to actively govern the topography of GBM matrix proteins. Expression of the a//3-DG complex was reported to be reduced in muscular dystrophies. and therefore a search for similar pathologic alterations in archival kidney biopsies from patients with MCN (it = 16) and FSGS (ni = 8) was conducted by quantitative immunoelectron microscopy. The density of a-DG on the podocyte's soles was significantly reduced to 25% in MCN, whereas it was not different in normal kidneys and FSGS. The expression of 3-DG was reduced to >50% in MCN, and was slightly increased in FSGS. Levels of DG expression returned to normal in MCN after steroid treatment (7 = 4). Expression of /3-integrin remained at normal levels in all conditions. These findings point to different potentially pathogenic mechanisms of foot process flattening in MCN and FSGS.
authors.affiliation: Institute for Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Austria.
authors.forename: Heinrich M
authors.initials: HM
authors.lastname: Regele
authors.affiliation: Institute for Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Austria.
authors.forename: Edith
authors.initials: E
authors.lastname: Fillipovic
authors.affiliation: Institute for Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Langer
authors.affiliation: Institute for Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Austria.
authors.forename: Helga
authors.initials: H
authors.lastname: Poczewki
authors.affiliation: Institute for Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Austria.
authors.forename: Ilse
authors.initials: I
authors.lastname: Kraxberger
authors.affiliation: Institute of Anatomy, Neuromuscular Research Department, University of Vienna, Vienna, Austria.
authors.forename: Reginald E
authors.initials: RE
authors.lastname: Bittner
authors.affiliation: Institute for Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Austria.
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
mesh_terms: D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values; D013256:Steroids / Q000627:therapeutic use; D014018:Tissue Distribution; D049411:Utrophin
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D013256:Steroids; D049411:Utrophin; D049030:Dystroglycans