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10.1152/ajprenal.00023.2012

http://scihub22266oqcxt.onion/10.1152/ajprenal.00023.2012
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suck abstract from ncbi


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pmid22791339      Am+J+Physiol+Renal+Physiol 2012 ; 303 (6): F821-30
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  • Endotoxemia alters tight junction gene and protein expression in the kidney #MMPMID22791339
  • Eadon MT; Hack BK; Xu C; Ko B; Toback FG; Cunningham PN
  • Am J Physiol Renal Physiol 2012[Sep]; 303 (6): F821-30 PMID22791339show ga
  • 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.
  • |Acute Disease[MESH]
  • |Animals[MESH]
  • |Endotoxemia/chemically induced/genetics/*metabolism[MESH]
  • |Gene Expression Regulation[MESH]
  • |Kidney/*metabolism/pathology[MESH]
  • |Lipopolysaccharides/toxicity[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Tight Junction Proteins/genetics/*metabolism[MESH]


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