TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis

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TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis

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dc.contributor.author Xu, Chang en_US
dc.contributor.author Chang, Anthony en_US
dc.contributor.author Hack, Bradley K. en_US
dc.contributor.author Eadon, Michael T. en_US
dc.contributor.author Alper, Seth L. en_US
dc.contributor.author Cunningham, Patrick N. en_US
dc.date.accessioned 2014-08-13T14:00:26Z
dc.date.issued 2013 en_US
dc.identifier.citation Xu, Chang, Anthony Chang, Bradley K. Hack, Michael T. Eadon, Seth L. Alper, and Patrick N. Cunningham. 2013. “TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.” Kidney international 85 (1): 10.1038/ki.2013.286. doi:10.1038/ki.2013.286. http://dx.doi.org/10.1038/ki.2013.286. en
dc.identifier.issn 0085-2538 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717608
dc.description.abstract Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration perm-selectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse. en
dc.language.iso en_US en
dc.relation.isversionof doi:10.1038/ki.2013.286 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834073/pdf/ en
dash.license LAA en_US
dc.subject acute kidney injury en
dc.subject fenestrae en
dc.subject albuminuria en
dc.subject endothelial cells en
dc.subject endothelial surface layer en
dc.subject lipopolysaccharide en
dc.title TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Kidney international en
dash.depositing.author Alper, Seth L. en_US
dc.date.available 2014-08-13T14:00:26Z

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