Cell polarity in human renal cystic disease

F. A. Carone, S. Nakamura, M. Caputo, R. Bacallao, W. J. Nelson, Y. S. Kanwar

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

BACKGROUND: In polycystic kidney disease (PKD), altered cellular polarity with mislocation of Na/K-ATPase, and net fluid secretion may have a role in cyst development and progression. EXPERIMENTAL DESIGN: Cell polarity was assessed in surgically excised human normal, autosomal dominant PKD, and acquired PKD occurring in end stage renal disease on long-term dialysis kidneys quick frozen (<5 minutes) or fixed to minimize ischemic changes. RESULTS: Findings were similar in autosomal dominant PKD and acquired PKD kidneys. By ultrastructure, in cysts, cells were polarized, however, their basement membranes were greatly thickened and reticulated. By immunohistology, in cell-lining cysts, Na/K-ATPase, fodrin, and ankyrin were localized primarily to basolateral cell membranes and uvomorulin was localized to lateral cell membranes. In about 25% of the cells, however, Na/K-ATPase was localized to the apical as well as the basolateral membranes. Both in autosomal dominant PKD and normal kidney cell monolayers in vitro, cationic ferritin was normally absorbed by apical endocytosis, and transferred to apical vacuoles and phagolysosomes. CONCLUSIONS: These findings indicate intact structural and functional polarity in cell-lining cysts; however, in about 25% of the cells, Na/K-ATPase, fodrin, and ankyrin are localized to apical and lateral cell membranes, probably due to cell dedifferentiation. The notable changes in the basement membranes of cysts suggest a key role for the extracellular matrix in the pathogenesis of PKD.

Original languageEnglish (US)
Pages (from-to)648-655
Number of pages8
JournalLaboratory Investigation
Volume70
Issue number5
StatePublished - 1994

Keywords

  • Ankyrin
  • Cationic Ferritin
  • Fodrin
  • Na,K-ATPase
  • Uvomorulin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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