PMID- 16339962
OWN - NLM
STAT- MEDLINE
DCOM- 20060124
LR  - 20220408
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 290
IP  - 1
DP  - 2006 Jan
TI  - Tight junction biology and kidney dysfunction.
PG  - F20-34
AB  - 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.
FAU - Lee, David B N
AU  - Lee DB
AD  - Division of Nephrology, Veterans Affairs Greater Los Angeles Healthcare System, 
      California, USA. dbnlee@ucla.edu
FAU - Huang, Edmund
AU  - Huang E
FAU - Ward, Harry J
AU  - Ward HJ
LA  - eng
GR  - 1R01DK/HD-51948/DK/NIDDK NIH HHS/United States
GR  - T32-DK-07789/DK/NIDDK NIH HHS/United States
GR  - T32-HL-07656/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Claudins)
RN  - 0 (Membrane Proteins)
RN  - 0 (TRPP Cation Channels)
RN  - 0 (claudin 16)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (WNK4 protein, human)
RN  - MRC5FX426I (claudin 6)
SB  - IM
MH  - Claudins
MH  - Fibrosis/etiology
MH  - Humans
MH  - Kidney Diseases/pathology/*physiopathology
MH  - Kidney Glomerulus/pathology
MH  - Membrane Proteins/genetics/metabolism/physiology
MH  - Models, Biological
MH  - Podocytes/pathology
MH  - Protein Serine-Threonine Kinases/physiology
MH  - Proteinuria/etiology/pathology
MH  - TRPP Cation Channels/metabolism
MH  - Tight Junctions/pathology/*physiology
RF  - 184
EDAT- 2005/12/13 09:00
MHDA- 2006/01/25 09:00
CRDT- 2005/12/13 09:00
PHST- 2005/12/13 09:00 [pubmed]
PHST- 2006/01/25 09:00 [medline]
PHST- 2005/12/13 09:00 [entrez]
AID - 290/1/F20 [pii]
AID - 10.1152/ajprenal.00052.2005 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2006 Jan;290(1):F20-34. doi: 
      10.1152/ajprenal.00052.2005.