Tight junction biology and kidney dysfunction

David B N Lee, Edmund Huang, Harry J. Ward

Research output: Contribution to journalArticle

Abstract

The epithelial tight junction (TJ) has three major functions. As a "gate," it serves as a regulatory barrier separating and maintaining biological fluid compartments of different composition. As a "fence," it generates and maintains the apicobasal polarity of cells that form the confluent epithelium. Finally, the TJ proteins form a trafficking and signaling platform that regulates cell growth, proliferation, differentiation, and dedifferentiation. Six examples are selected that illustrate the emerging link between TJ dysfunction and kidney disease. First, the glomerular slit diaphragm (GSD) is evolved, in part, from the TJ and, on maturation, exhibits all three functions of the TJ. GSD dysfunction leads to proteinuria and, in some instances, podocyte dedifferentiation and proliferation. Second, accumulating evidence supports epithelial-mesenchymal transformation (EMT) as a major player in renal fibrosis, the final common pathway that leads to end-stage renal failure. EMT is characterized by a loss of cell-cell contact and apicobasal polarity, which are hallmarks of TJ dysfunction. Third, in autosomal dominant polycystic kidney disease, mutations of the polycystins may disrupt their known interactions with the apical junction complex, of which the TJ is a major component. This can lead to disturbances in epithelial polarity regulation with consequent abnormal tubulogenesis and cyst formation. Fourth, evidence for epithelial barrier and polarity dysregulation in the pathogenesis of ischemic acute renal failure will be summarized. Fifth, the association between mutations of paracellin-1, the first TJ channel identified, and clinical disorders of magnesium and calcium wasting and bovine renal fibrosis will be used to highlight an integral TJ protein that can serve multiple TJ functions. Finally, the role of WNK4 protein kinase in shunting chloride across the TJ of the distal nephron will be addressed.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume290
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

Tight Junctions
Kidney
Tight Junction Proteins
Epithelial-Mesenchymal Transition
Diaphragm
Fibrosis
TRPP Cation Channels
Autosomal Dominant Polycystic Kidney
Podocytes
Cell Polarity
Mutation
Nephrons
Kidney Diseases
Proteinuria
Acute Kidney Injury
Protein Kinases
Magnesium
Chronic Kidney Failure
Cysts
Chlorides

Keywords

  • Kidney disease
  • Zonula occludens

ASJC Scopus subject areas

  • Physiology

Cite this

Tight junction biology and kidney dysfunction. / Lee, David B N; Huang, Edmund; Ward, Harry J.

In: American Journal of Physiology - Renal Physiology, Vol. 290, No. 1, 01.2006.

Research output: Contribution to journalArticle

Lee, David B N ; Huang, Edmund ; Ward, Harry J. / Tight junction biology and kidney dysfunction. In: American Journal of Physiology - Renal Physiology. 2006 ; Vol. 290, No. 1.
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