Endotoxemia alters tight junction gene and protein expression in the kidney

作者：Eadon Michael T^*; Hack Bradley K; Xu Chang; Ko Benjamin; Toback F Gary; Cunningham Patrick N

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2012, 303(6): F821-F830.

DOI：10.1152/ajprenal.00023.2012

• claudin
• LPS endotoxin
• acute kidney injury
• occludin
• ZO-1

Eadon MT, Hack BK, Xu C, Ko B, Toback FG, Cunningham PN. Endotoxemia alters tight junction gene and protein expression in the kidney. Am J Physiol Renal Physiol 303: F821-F830, 2012. First published July 11, 2012; doi:10.1152/ajprenal.00023.2012.-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.

• 出版日期2012-9