title: Formation of tight junctions between neighboring podocytes is an early ultrastructural feature in experimental crescentic glomerulonephritis.
abstract: OBJECTIVE
  In crescentic glomerulonephritis (CGN), the development of cellular bridges between podocytes and parietal epithelial cells (PECs) triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN.
  
  
  METHODS
  Transmission electron microscopy (TEM) was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN) from day 1 to day 14. Morphometric analysis was conducted on randomly selected glomeruli captured on TEM digital images.
  
  
  RESULTS
  On day 1 of NSN, there was widespread formation of focal contacts between the cell bodies of neighboring podocytes, and tight junctions were evident at the site of cell-to-cell contact. This was confirmed by the increased expression of the tight junction molecule, zonula occludens-1 (ZO-1), which localized to the points of podocyte cell-cell body contact. On day 2, the interpodocyte distance decreased and the glomerular basement membrane thickness increased. Foot process effacement (FPE) was segmental on day 3 and diffuse by day 5, accompanied by the formation of podocyte cellular bridges with Bowman's capsule, as confirmed by a decrease in podocyte-to-PEC distance. Fibrinoid necrosis and cellular crescents were evident in all glomeruli by days 7 and 14. In vitro, the exposure of podocytes to macrophage-conditioned media altered cellular morphology and caused an intracellular redistribution of ZO-1.
  
  
  CONCLUSIONS
  The formation of tight junctions between podocytes is an early ultrastructural abnormality in CGN, preceding FPE and podocyte bridge formation and occurring in response to inflammatory injury. Podocyte-to-podocyte tight junction formation may be a compensatory mechanism to maintain the integrity of the glomerular filtration barrier following severe endocapillary injury.
authors.affiliation: Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney.
authors.forename: Lena
authors.initials: L
authors.lastname: Succar
authors.affiliation: Electron Microscopy Laboratory, Institute of Clinical Pathology and Medical Research, Westmead Hospital.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Boadle
authors.affiliation: Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney; Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, NSW, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Harris
authors.affiliation: Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney; Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, NSW, Australia.
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Rangan
keywords: crescent; glomerular; inflammation; zonula occludens