Attenuated expression of epithelial cell adhesion molecules in murine polycystic kidney disease

M. V. Rocco, E. G. Neilson, J. R. Hoyer, F. N. Ziyadeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Polycystic kidney disease is an inherited disorder of parenchymal structure that leads to renal failure. Cysts begin as focal dilations in proximal tubules and collecting ducts, giving rise to cyst walls lined by a phenotypically disturbed epithelium that expresses dysfunctional transport and matrix proteins. We used an mRNA search protocol to probe efficiently for tissue-specific disturbances that might underlie the formation of cysts. This search assessed the relative abundance of transcripts encoding a variety of growth factors (transforming growth factor-β1, interleukin-6, tumor necrosis factor, and endothelin-1), structural proteins (collagen IV, nidogen, fibronectin, and laminins A and B1), and cell adhesion molecules (CAMs; E-cadherin, N-CAM, laminin receptor, and fibronectin receptor) in the cystic kidneys of cpk/cpk mice and uncovered a previously unrecognized early reduction in mRNA encoding N-CAM (54%) and E-cadherin (56%) (n = 5; P < 0.001). Levels of transcripts for growth factors, structural proteins, and for fibronectin and laminin receptors in normal and cystic kidneys were generally similar. The reduction in transcripts for N-CAM and E-cadherin in kidneys from cystic mice was not observed in autologous liver. The immunofluorescent staining of cystic kidneys confirmed that the decrease in N-CAM and E-cadherin was generally confined to regions abundant in developing cystic epithelium. The presence of both N-CAM and E-cadherin appears to guide the sequential differentiation and polarization of normal renal epithelium, and their attenuated expression in the kidney of cpk/ cpk mice may be a material factor contributing to the pathogenesis of cyst formation.

Original languageEnglish (US)
Pages (from-to)F679-F686
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume262
Issue number4 31-4
StatePublished - 1992

Keywords

  • E-cadherin (uvomorulin)
  • Extracellular matrix
  • N-cell adhesion molecule
  • Polymerase chain reaction
  • cpk/cpk mouse

ASJC Scopus subject areas

  • Physiology

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