ArticleAmerican journal of physiology. Renal physiology2016
Peptidyl arginine deiminase-4-deficient mice are protected against kidney and liver injury after renal ischemia and reperfusion.
Article in American journal of physiology. Renal physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 56 citations in OpenAlex.
- Review
- Neutrophil extracellular traps and acute kidney injury: a narrative review.Frontiers in immunology · 2026Review
- Burns: The "Fuse" That Ignites Organ Crisis - A Narrative Review of Mechanisms and Crosstalk in Post-Burn MODS.Journal of inflammation research · 2026Review
- Mac-1 Promotes Neutrophil Extracellular Traps Formation via ERK Phosphorylation in Renal Ischemia-Reperfusion Injury.Inflammation · 2025Article
- Myeloid Cells in Acute Kidney Injury.Seminars in nephrology · 2025Review
- Peptidylarginine deiminase 4 deficiency alleviates hypoxia/reoxygenation-induced cardiomyocyte injury.PloS one · 2025Article
- Lymphocytes and innate immune cells in acute kidney injury and repair.Nature reviews. Nephrology · 2024Review
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.JCI insight · 2023Article
- GADD45A and GADD45B as Novel Biomarkers Associated with Chromatin Regulators in Renal Ischemia-Reperfusion Injury.International journal of molecular sciences · 2023Article
- Chemistry, Biosynthesis and Pharmacology of Streptonigrin: An Old Molecule with Future Prospects for New Drug Design, Development and Therapy.Drug design, development and therapy · 2023Review
- The role of neutrophil extracellular traps in cancer progression, metastasis and therapy.Experimental hematology & oncology · 2022Review
- Inhibition of Netosis with PAD Inhibitor Attenuates Endotoxin Shock Induced Systemic Inflammation.International journal of molecular sciences · 2022Article
- PAD4 silencing inhibits inflammation whilst promoting trophoblast cell invasion and migration by inactivating the NEMO/NF-κB pathway.Experimental and therapeutic medicine · 2022Article
- CXCL1-Triggered PAD4 Cytoplasmic Translocation Enhances Neutrophil Adhesion through Citrullination of PDIA1.Journal of atherosclerosis and thrombosis · 2022Article
- Review
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- Recent Approaches to Targeting Canonical NFJournal of the American Society of Nephrology : JASN · 2021Review
- The Role of Neutrophil Extracellular Traps in Cancer.Frontiers in oncology · 2021Review
- Renal proximal tubular NEMO plays a critical role in ischemic acute kidney injury.JCI insight · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We previously demonstrated that renal peptidyl arginine deiminase-4 (PAD4) is induced after renal ischemia and reperfusion (I/R) injury and exacerbates acute kidney injury (AKI) by increasing the renal tubular inflammatory response. Here, we tested whether genetic ablation of PAD4 attenuates renal injury and inflammation after I/R in mice. After renal I/R, PAD4 wild-type mice develop severe AKI with large increases in plasma creatinine, neutrophil infiltration, as well as significant renal tubular necrosis, apoptosis, and proinflammatory cytokine generation. In contrast, PAD4-deficient mice are protected against ischemic AKI with reduced real tubular neutrophil infiltration, renal tubular necrosis, and apoptosis. In addition, hepatic injury and inflammation observed in PAD4 wild-type mice after renal I/R are significantly attenuated in PAD4-deficient mice. We also show that increased renal tubular PAD4 expression after renal I/R is associated with translocation of PAD4 from the nucleus to the cytosol. Consistent with PAD4 cytosolic translocation, we show increased renal tubular cytosolic peptidyl-citrullination after ischemic AKI. Mechanistically, recombinant PAD4 treatment increased nuclear translocation of NF-κB in cultured human as well as murine proximal tubule cells that is inhibited by a PAD4 inhibitor (2-chloroamidine). Taken together, our studies further support the hypothesis that renal tubular PAD4 plays a critical role in renal I/R injury by increasing the renal tubular inflammatory response and neutrophil infiltration after renal I/R perhaps by interacting with the proinflammatory transcription factor NF-κB in the cytosol and promoting its nuclear translocation.
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