Endotoxemia alters tight junction gene and protein expression in the kidney

Michael Eadon, Bradley K. Hack, Chang Xu, Benjamin Ko, F. Gary Toback, Patrick N. Cunningham

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Intact tight junctional (TJ) proteins are required for tubular ion transport and waste excretion. Disruption of TJs may contribute to a decreased glomerular filtration rate in acute kidney injury (AKI) via tubular backleak. The effect of LPS-mediated AKI on murine TJs has not been studied extensively. We hypothesized LPS endotoxin administration to mice would disrupt tubular TJ proteins including zonula occludens-1 (ZO-1), occludin, and claudins. ZO-1 and occludin immunofluorescence 24 h post-LPS revealed a marked change in localization from the usual circumferential fencework pattern to one with substantial fragmentation. Renal ZO-1 expression was significantly reduced 24 h after LPS (decrease of 56.1 ± 7.4%, P < 0.001), with subsequent recovery. ZO-1 mRNA expression was increased 24 h post-LPS (4.34 ± 0.87-fold, P = 0.0019), suggesting disruption of ZO-1 protein is not mediated by transcriptional regulation, but rather by degradation or changes in translation. Similarly, claudin-4 protein expression was decreased despite elevated mRNA. LPS administration resulted in dephosphorylation of occludin and fragmented tubular redistribution. Protein expression of claudin-1, and -3 was increased after LPS. ZO-1, occludin, and claudin-1, -3, and -4 gene expression were increased 48 h after LPS, suggesting a renal response to strengthen TJs following injury. Interestingly, reduced mRNA expression was found only for claudin-8. This study provides further support that LPS-induced AKI is associated with structural injury and is not merely due to hemodynamic changes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number6
DOIs
StatePublished - Sep 15 2012
Externally publishedYes

Fingerprint

Occludin
Tight Junction Proteins
Endotoxemia
Tight Junctions
Claudin-3
Zonula Occludens-1 Protein
Claudins
Claudin-1
Acute Kidney Injury
Kidney
Gene Expression
Messenger RNA
Proteins
Claudin-4
Ion Transport
Wounds and Injuries
Glomerular Filtration Rate
Endotoxins
Fluorescent Antibody Technique
Hemodynamics

Keywords

  • Acute kidney injury
  • Claudin
  • LPS endotoxin
  • Occludin
  • ZO-1

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Endotoxemia alters tight junction gene and protein expression in the kidney. / Eadon, Michael; Hack, Bradley K.; Xu, Chang; Ko, Benjamin; Gary Toback, F.; Cunningham, Patrick N.

In: American Journal of Physiology - Renal Physiology, Vol. 303, No. 6, 15.09.2012.

Research output: Contribution to journalArticle

Eadon, Michael ; Hack, Bradley K. ; Xu, Chang ; Ko, Benjamin ; Gary Toback, F. ; Cunningham, Patrick N. / Endotoxemia alters tight junction gene and protein expression in the kidney. In: American Journal of Physiology - Renal Physiology. 2012 ; Vol. 303, No. 6.
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