BROWSE

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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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NF-kappa B modulates aquaporin-2 transcription in renal collecting duct principal cells

Cited 24 times inthomson ciCited 19 times inthomson ci
Title
NF-kappa B modulates aquaporin-2 transcription in renal collecting duct principal cells
Author
Hasler, UdoLeroy, ValeeieJeon, Un SilBouley, RichardDimitrov, MitkoKim, Jeong AhBrown, DennisKwon, H. MooMartin, Pierre-YvesFeraille, Eric
Keywords
INDUCED NEPHROTIC SYNDROME; ENHANCER-BINDING PROTEIN; WATER CHANNEL EXPRESSION; DOWN-REGULATION; NULL MICE; ACTIVATION; MECHANISM; GENE; HYPERTONICITY; PERMEABILITY
Issue Date
200810
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.42, pp.28095 - 28105
Abstract
Renal tubulo-interstitial inflammation is frequently associated with polyuria and urine concentration defects. This led us to investigate the effects of the major pro-inflammatory nuclear factor kappa B (NF-kappa B) pathway on aquaporin 2 (AQP2) expression by the collecting duct. Using immortalized collecting duct principal cells (mpkCCD(c14)), we found that, acting independently of vasopressin, activation of NF-kappa B by lipopolysaccharide (LPS) decreased AQP2 mRNA and protein levels in a time-and dose-dependent manner but did not decrease AQP2 mRNA stability. Consistently, constitutively active I kappa B kinase beta decreased AQP2 expression. The LPS-induced decrease in AQP2 mRNA levels was confirmed in rat kidney slices and was reproduced both under conditions of elevated cAMP concentration and V-2 receptor antagonism. Computer analysis of the AQP2 promoter revealed two putative kappa B elements. Mutation of either kappa B element abolished the LPS-induced decrease of luciferase activity in cells expressing AQP2 promoter-luciferase plasmid constructs. Chromatin immunoprecipitation revealed that LPS challenge decreased p65, increased p50 and p52, and had no effect on RelB and c-Rel binding to kappa B elements of the AQP2 promoter. RNA-mediated interference silencing of p65, p50, and p52 confirmed controlled AQP2 transcription by these NF-kappa B subunits. We additionally found that hypertonicity activated NF-kappa B in mpkCCD(c14) cells, an effect that may counteract the Tonicity-responsive enhancer binding protein (TonEBP)-dependent increase in AQP2 gene transcription. Taken together, these findings indicate that NF-kappa B is an important physiological regulator of AQP2 transcription.
URI
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DOI
http://dx.doi.org/10.1074/jbc.M708350200
ISSN
0021-9258
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