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dc.contributor.authorXu, Changen_US
dc.contributor.authorChang, Anthonyen_US
dc.contributor.authorHack, Bradley K.en_US
dc.contributor.authorEadon, Michael T.en_US
dc.contributor.authorAlper, Seth L.en_US
dc.contributor.authorCunningham, Patrick N.en_US
dc.date.accessioned2014-08-13T14:00:26Z
dc.date.issued2013en_US
dc.identifier.citationXu, 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.issn0085-2538en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12717608
dc.description.abstractSevere 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.isoen_USen
dc.relation.isversionofdoi:10.1038/ki.2013.286en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834073/pdf/en
dash.licenseLAAen_US
dc.subjectacute kidney injuryen
dc.subjectfenestraeen
dc.subjectalbuminuriaen
dc.subjectendothelial cellsen
dc.subjectendothelial surface layeren
dc.subjectlipopolysaccharideen
dc.titleTNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalKidney internationalen
dash.depositing.authorAlper, Seth L.en_US
dc.date.available2014-08-13T14:00:26Z
dc.identifier.doi10.1038/ki.2013.286*
dash.contributor.affiliatedAlper, Seth


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