Original Paper

Tight junction composition is altered in the epithelium of polycystic kidneys†

  1. ASL Yu1,2,*,
  2. SA Kanzawa1,
  3. A Usorov1,
  4. IS Lantinga-van Leeuwen3,
  5. DJM Peters3

Article first published online: 13 JUN 2008

DOI: 10.1002/path.2392

Issue

The Journal of Pathology

The Journal of Pathology

Volume 216, Issue 1, pages 120–128, September 2008

Additional Information

How to Cite

Yu, A., Kanzawa, S., Usorov, A., Lantinga-van Leeuwen, I. and Peters, D. (2008), Tight junction composition is altered in the epithelium of polycystic kidneys. The Journal of Pathology, 216: 120–128. doi: 10.1002/path.2392

Author Information

  1. 1

    Division of Nephrology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA

  2. 2

    Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California, USA

  3. 3

    Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, The Netherlands

*University of Southern California Keck School of Medicine, Division of Nephrology, 2025 Zonal Avenue, RMR 406, Los Angeles, CA 90089, USA.

  1. †

    No conflicts of interest were declared.

Publication History

  1. Issue published online: 4 AUG 2008
  2. Article first published online: 13 JUN 2008
  3. Accepted manuscript online: 13 JUN 2008 12:00AM EST
  4. Manuscript Accepted: 4 JUN 2008
  5. Manuscript Revised: 3 JUN 2008
  6. Manuscript Received: 30 APR 2008

Funded by

  • National Institutes of Health. Grant Numbers: DK062283, DK48522
  • Dutch Kidney Foundation. Grant Number: C05-2132 to DJMP

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (478K)

Keywords:

  • renal cysts;
  • tight junctions;
  • claudins;
  • autosomal dominant polycystic kidney disease

Abstract

Kidney cysts in autosomal dominant polycystic kidney disease (ADPKD) undergo progressive enlargement together with luminal fluid secretion. This involves active, uphill transcellular Cl− transport which drives passive Na+ and water secretion. Implicit in this mechanism is the assumption that the paracellular permeability of the cyst epithelium to Cl− must be very low. Claudins are tight junction (TJ) transmembrane proteins that determine the ion selectivity of paracellular barriers. The aim of this study was to determine the expression and localization of claudins within renal cysts in a mouse hypomorphic model of ADPKD and in human patients. We found that the majority of cysts were of collecting duct origin. Claudins normally expressed in collecting duct (3, 4, 7, 8, and 10) were found in small cysts. However, only claudin-7 persisted at substantive levels in the dedifferentiated epithelium of large, presumably late-stage cysts, where it was localized both at the TJ and basolaterally. The constitutively expressed TJ proteins, ZO-1 and occludin, were also abundantly expressed and correctly localized, suggesting that the basic infrastructure of the TJ is preserved. A previous study suggested that claudin-7 may function as a paracellular Cl− barrier. We postulate that the role of claudin-7 in ADPKD is to seal the paracellular route in Cl−-secreting cyst epithelium, preventing backleak of Cl−, and that it thereby plays a permissive role in fluid secretion and cyst growth. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

View Full Article with Supporting Information (HTML) Get PDF (478K)