ArticleAmerican journal of physiology. Renal physiology2019
Peptidyl arginine deiminase-4 exacerbates ischemic AKI by finding NEMO.
Article in American journal of physiology. Renal physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Review
- NET-mediated immunothrombosis in ischemic stroke: pathobiology, biomarkers, and therapeutic targeting.Thrombosis journal · 2026Review
- Review
- miR-181c, a potential mediator for acute kidney injury in a burn rat model with following sepsis.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2023Article
- CXCL1-Triggered PAD4 Cytoplasmic Translocation Enhances Neutrophil Adhesion through Citrullination of PDIA1.Journal of atherosclerosis and thrombosis · 2022Article
- PAD4 silencing inhibits inflammation whilst promoting trophoblast cell invasion and migration by inactivating the NEMO/NF-κB pathway.Experimental and therapeutic medicine · 2022Article
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury.Frontiers in medicine · 2022Review
- Recent Approaches to Targeting Canonical NFJournal of the American Society of Nephrology : JASN · 2021Review
- RGD Peptide and PAD4 Inhibitor-Loaded Gold Nanorods for Chemo-Photothermal Combined Therapy to Inhibit Tumor Growth, Prevent Lung Metastasis and Improve Biosafety.International journal of nanomedicine · 2021Article
- Renal proximal tubular NEMO plays a critical role in ischemic acute kidney injury.JCI insight · 2020Article
- Putative Roles for Peptidylarginine Deiminases in COVID-19.International journal of molecular sciences · 2020Article
- Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.International journal of molecular sciences · 2020Article
- Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury.Mediators of inflammation · 2020Article
- Mechanisms and therapeutic targets of ischemic acute kidney injury.Kidney research and clinical practice · 2019Review
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Authors and funding
5 authors.
Funding
Abstract
Peptidyl arginine deiminase-4 (PAD4) catalyzes the conversion of peptidylarginine residues to peptidylcitrulline. We have previously shown that kidney ischemia-reperfusion (I/R) injury increases renal proximal tubular PAD4 expression and activity. Furthermore, kidney PAD4 plays a critical role in ischemic acute kidney injury (AKI) by promoting renal tubular inflammation, neutrophil infiltration, and NF-κB activation. However, the mechanisms of PAD4-mediated renal tubular inflammation and NF-κB activation after I/R remain unclear. Here, we show that recombinant PAD4 preferentially citrullinates recombinant IKKγ [also called NF-κB essential modulator (NEMO)] over recombinant IKKα or IKKβ. Consistent with this finding, PAD4 citrullinated renal proximal tubular cell IKKγ and promoted NF-κB activation via IκBα phosphorylation in vitro. NEMO inhibition with a selective NEMO-binding peptide attenuated PAD4-mediated proinflammatory cytokine mRNA induction in HK-2 cells. Moreover, NEMO inhibition did not affect proximal tubular cell survival, proliferation, or apoptosis, unlike global NF-κB inhibition. In vivo, NEMO-binding peptide treatment protected against ischemic AKI. Finally, NEMO-binding peptide attenuated recombinant PAD4-mediated exacerbation of ischemic AKI, renal tubular inflammation, and apoptosis. Taken together, our results show that PAD4 exacerbates ischemic AKI and inflammation by promoting renal tubular NF-κB activity and inflammation via NEMO citrullination. Targeting NEMO activation may serve as a potential therapy for this devastating clinical problem.
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