Renal proximal tubular NEMO plays a critical role in ischemic acute kidney injury Journal Article

Authors: Han, S. J.; Williams, R. M.; Kim, M.; Heller, D. A.; D'Agati, V.; Schmidt-Supprian, M.; Lee, H. T.
Article Title: Renal proximal tubular NEMO plays a critical role in ischemic acute kidney injury
Abstract: We determined that renal proximal tubular (PT) NF-κB essential modulator (NEMO) plays a direct and critical role in ischemic acute kidney injury (AKI) using mice lacking renal PT NEMO and by targeted renal PT NEMO inhibition with mesoscale nanoparticle-encapsulated NEMO binding peptide (NBP MNP). We subjected renal PT NEMO-deficient mice, WT mice, and C57BL/6 mice to sham surgery or 30 minutes of renal ischemia and reperfusion (IR). C57BL/6 mice received NBP MNP or empty MNP before renal IR injury. Mice treated with NBP MNP and mice deficient in renal PT NEMO were protected against ischemic AKI, having decreased renal tubular necrosis, inflammation, and apoptosis compared with control MNP-treated or WT mice, respectively. Recombinant peptidylarginine deiminase type 4 (rPAD4) targeted kidney PT NEMO to exacerbate ischemic AKI in that exogenous rPAD4 exacerbated renal IR injury in WT mice but not in renal PT NEMO-deficient mice. Furthermore, rPAD4 upregulated proinflammatory cytokine mRNA and NF-κB activation in freshly isolated renal proximal tubules from WT mice but not from PT NEMO-deficient mice. Taken together, our studies suggest that renal PT NEMO plays a critical role in ischemic AKI by promoting renal tubular inflammation, apoptosis, and necrosis.
Keywords: inflammation; pharmacology
Journal Title: JCI Insight
Volume: 5
Issue: 19
ISSN: 2379-3708
Publisher: Amer Soc Clinical Investigation Inc  
Date Published: 2020-10-02
Start Page: e139246
Language: English
DOI: 10.1172/jci.insight.139246
PUBMED: 32941183
PROVIDER: scopus
PMCID: PMC7566738
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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MSK Authors
  1. Daniel Alan Heller
    97 Heller