Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis

Extensive flattening of podocyte foot processes and increased permeability of the glomerular capillary filter are the major pathologic features of min imal 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 pr ocess flattening. Thus far, alpha(3) beta(1)-integrin was localized to basa l cell membrane domains. In this report, alpha- and beta-dystroglycan (DG) were detected at precisely the same location by immunoelectron microscopy, and the presence of alpha- and beta-DG chains was confirmed by immunoblotti ng on isolated human glomeruli. Because the major DG binding partners in th e GEM (laminin, agrin, perlecan), and the intracellular dystrophin analogue utrophin are also present in glomeruli, it appears that podocytes adhere t o the GEM via DG complexes, similar to muscle fibers in which actin is link ed via dystrophin and DG to the extracellular matrix. As with muscle cells, it is therefore plausible that podocytes use precisely actin:guided DG com plexes at their "soles" to actively govern the topography of GEM matrix pro teins. Expression of the alpha/beta-DG complex was reported to be reduced i n muscular dystrophies, and therefore a search for similar pathologic alter ations in archival kidney biopsies from patients with MCN (n = 16) and FSGS (n = 8) was conducted by quantitative immunoelectron microscopy, The densi ty of cr-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 o f beta-DG was reduced to >50% in MCN, and was slightly increased in FSGS. L evels of DG expression returned to normal in MCN after steroid treatment (n = 4). Expression of beta(1)-integrin remained at normal levels in all cond itions. These findings point to different potentially pathogenic mechanisms of foot process flattening in MCN and FSGS.