A new function for parietal epithelial cells: a second glomerular barrier

Am J Physiol Renal Physiol. 2009 Dec;297(6):F1566-74. doi: 10.1152/ajprenal.00214.2009. Epub 2009 Sep 30.


The functional role of glomerular parietal epithelial cells (PECs) remains poorly understood. To test the hypothesis that PECs form an impermeable barrier to filtered protein through the formation of tight junctions (TJ), studies were performed in normal animals and in the anti-glomerular basement membrane (GBM) model of crescentic nephritis. Electron microscopy showed well-defined TJ between PECs in normal mice, which no longer could be identified when these cells became extensively damaged or detached from their underlying Bowman's basement membrane. The TJ proteins claudin-1, zonula occludens-1, and occludin stained positive in PECs; however, staining decreased in anti-GBM disease. To show that these events were associated with increased permeability across the PEC-Bowman's basement membrane barrier, control and diseased animals were injected intravenously with either Texas red-conjugated dextran (3 kDa) or ovalbumin (45 kDa) tracers. As expected, both tracers were readily filtered across the glomerular filtration barrier and taken up by proximal tubular cells. However, when the glomerular filtration barrier was injured in anti-GBM disease, tracers were taken up by podocytes and PECs. Moreover, tracers were also detected between PECs and the underlying Bowman's basement membrane, and in many instances were detected in the extraglomerular space. We propose that together with its underlying Bowman's basement membrane, the TJ of PECs serve as a second barrier to protein. When disturbed following PEC injury, the increase in permeability of this layer to filtered protein is a mechanism underlying periglomerular inflammation characteristic of anti-GBM disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Anti-Glomerular Basement Membrane Disease / complications*
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Bowman Capsule / metabolism
  • Bowman Capsule / pathology
  • Cell Line
  • Claudin-1
  • Embryonic Development
  • Epithelial Cells / metabolism
  • Glomerular Filtration Rate
  • Humans
  • Kidney Glomerulus / embryology
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Nephritis / etiology*
  • Nephritis / metabolism*
  • Occludin
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / metabolism
  • Permeability
  • Phosphoproteins / metabolism
  • Podocytes / metabolism
  • Rats
  • Tight Junctions / metabolism
  • Tight Junctions / ultrastructure
  • Zonula Occludens-1 Protein


  • CLDN1 protein, human
  • Claudin-1
  • Cldn1 protein, mouse
  • Cldn1 protein, rat
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Ocln protein, mouse
  • Ocln protein, rat
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Pax8 protein, mouse
  • Phosphoproteins
  • TJP1 protein, human
  • Tjp1 protein, mouse
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein