title: Claudin 1 and nephrin label cellular crescents in diabetic glomerulosclerosis.
abstract: Cellular crescents are typically inflammatory and associated with rapidly progressive glomerulonephritis. Their pathogenesis involves glomerular basement membrane rupture due to circulating or intrinsic factors. Crescents associated with diabetic glomerulosclerosis are rarely reported. Furthermore, the nature of cells forming crescents in diabetes is unknown. To investigate the nature of crescents in diabetes, we examined renal biopsies from diabetic patients with nodular glomerulosclerosis and crescents (n = 2), diabetes without crescents (n = 5), nondiabetic renal biopsies (n = 3), and crescentic glomerulonephritis with inflammatory crescents (n = 5). Electron microscopy and confocal immunofluorescence analysis with antibodies against nephrin (a podocyte marker) and claudin 1 (parietal epithelial cell marker) were performed. Diabetic glomeruli with crescents contained a mixture of crescentic cells expressing either claudin 1 (11 ± 1.4 cells/glomerulus) or nephrin (5.5 ± 3.0 cells/glomerulus). Rare crescentic cells coexpressed nephrin and claudin 1 (2.5 ± 1.6 cells/glomerulus). In contrast, inflammatory crescents were almost exclusively composed of claudin 1-positive cells (25 ± 5.3 cells/glomerulus). Cells coexpressing claudin 1 and nephrin were absent in inflammatory crescents and all cases without crescents. Electron microscopy showed podocyte bridge formation between the glomerular basement membrane and parietal basement membrane but no glomerular basement membrane rupture as in inflammatory crescents. Crescents in diabetes may occur in diabetes in the absence of a secondary etiology and are composed of a mixture of parietal epithelial cells and visceral podocytes. Cells coexpressing parietal epithelial and podocyte markers suggest that parietal epithelial cells may transdifferentiate into podocytes in response to severe glomerular injury.
authors: Washington University School of Medicine, Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, St Louis, MO, USA. Electronic address: gautj@path.wustl.edu.
authors: Joseph P
authors: JP
authors: Gaut
authors: Washington University School of Medicine, Department of Medicine, Division of Nephrology, St Louis, MO 63110, USA.
authors: Masato
authors: M
authors: Hoshi
authors: Washington University School of Medicine, Department of Medicine, Division of Nephrology, St Louis, MO 63110, USA.
authors: Sanjay
authors: S
authors: Jain
authors: Washington University School of Medicine, Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, St Louis, MO, USA. Electronic address: liapis@path.wustl.edu.
authors: Helen
authors: H
authors: Liapis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D062445:Claudin-1; D008565:Membrane Proteins; C113267:nephrin
keywords: Claudin 1; Crescent; Diabetes; Nephrin; Parietal; Podocyte