ArticleJCI insight2020
Peptidylarginine deiminase 2 has potential as both a biomarker and therapeutic target of sepsis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification.Cell death & disease · 2023Pooled it
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- Integrative metabolite-protein interaction networks reveal potential pathways and biomarkers in sepsis.BMC infectious diseases · 2026Article
- Inhibition of PADI2-mediated vimentin citrullination alleviates silica-induced pulmonary fibrosis in mice.Particle and fibre toxicology · 2026Article
- Role of peptidylarginine deiminase 2 in a murine model of traumatic brain injury.The journal of trauma and acute care surgery · 2026Article
- Interleukin-33 Promotes Neutrophil Extracellular Trap Formation To Aggravate Renal Ischemia-Reperfusion Injury Through ST2/PI3K/Akt and ST2/PAD4 Pathways.Inflammation · 2026Article
- Roles of peptidylarginine deiminase (PAD) and protein citrullination in viral infections.Frontiers in microbiology · 2026Review
- Neutrophil extracellular traps in the animal model of adenine-induced chronic kidney disease.PloS one · 2026Article
- Periodontitis Leads to Systemic Bone Loss through Neutrophil Reprogramming.Journal of dental research · 2026Article
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Sex-dependent effects of peptidylarginine deiminases on neutrophil function and long-term outcomes after spinal cord injury.Experimental neurology · 2025Article
- PADI2 exacerbates Mycoplasma ovipneumoniae-induced lung injury in sheep by suppressing M2 macrophage polarization.Veterinary research · 2025Article
- Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025Review
- Article
- CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.Pharmaceutics · 2025Review
- Peptidylarginine Deiminase 4 Deficiency Suppresses Neutrophil Extracellular Trap Formation and Ameliorates Elastase-Induced Emphysema in Mouse Lung.International journal of molecular sciences · 2025Article
- Citrullination of NF-κB p65 by PAD2 as a Novel Therapeutic Target for Modulating Macrophage Polarization in Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Macrophage pyroptosis and its crucial role in ALI/ARDS.Frontiers in immunology · 2025Review
- Loss of PADI2 and PADI4 ameliorates sepsis-induced acute lung injury by suppressing NLRP3+ macrophages.JCI insight · 2024Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes that are involved in a variety of human disorders, including cancer and autoimmune diseases. Although targeting PAD4 has shown no benefit in sepsis, the role of PAD2 remains unknown. Here, we report that PAD2 is engaged in sepsis and sepsis-induced acute lung injury in both human patients and mice. Pad2-/- or selective inhibition of PAD2 by a small molecule inhibitor increased survival and improved overall outcomes in mouse models of sepsis. Pad2 deficiency decreased neutrophil extracellular trap (NET) formation. Importantly, Pad2 deficiency inhibited Caspase-11-dependent pyroptosis in vivo and in vitro. Suppression of PAD2 expression reduced inflammation and increased macrophage bactericidal activity. In contrast to Pad2-/-, Pad4 deficiency enhanced activation of Caspase-11-dependent pyroptosis in BM-derived macrophages and displayed no survival improvement in a mouse sepsis model. Collectively, our findings highlight the potential of PAD2 as an indicative marker and therapeutic target for sepsis.
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Registered trials
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