ArticleAmerican journal of physiology. Renal physiology2018
ATP induces PAD4 in renal proximal tubule cells via P2X7 receptor activation to exacerbate ischemic AKI.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- [Electroacupuncture Alleviates Acute Kidney Injury in Septic Mice By Inhibiting the P2RX7/NLRP3 Signaling Pathway].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- Research progress on damage-associated molecular patterns in acute kidney injury.Frontiers in immunology · 2025Review
- dsHMGB1, released from IL-17A-induced pyroptotic prostate epithelial cells, drives M1 polarization by promoting Pfkp-mediated glycolysis via Jak2/Stat1 transcription in experimental autoimmune prostatitis.International journal of biological sciences · 2025Article
- Activation of Purinergic P2Y2 Receptor Protects the Kidney Against Renal Ischemia and Reperfusion Injury in Mice.International journal of molecular sciences · 2024Article
- Molecular insights into P2X signalling cascades in acute kidney injury.Purinergic signalling · 2024Review
- P2X7R Modulates NEK7-NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD-mediated Prostate Epithelial Cell Pyroptosis.International journal of biological sciences · 2024Article
- P2 purinergic receptor dysregulation in urologic disease.Purinergic signalling · 2022Review
- Control of Directed Cell Migration after Tubular Cell Injury by Nucleotide Signaling.International journal of molecular sciences · 2022Article
- Blocking connexin 43 and its promotion of ATP release from renal tubular epithelial cells ameliorates renal fibrosis.Cell death & disease · 2022Article
- Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury.Frontiers in medicine · 2022Review
- Adenosine Triphosphate Accumulated Following Cerebral Ischemia Induces Neutrophil Extracellular Trap Formation.International journal of molecular sciences · 2020Article
- Renal proximal tubular NEMO plays a critical role in ischemic acute kidney injury.JCI insight · 2020Article
- Selective nanoparticle-mediated targeting of renal tubular Toll-like receptor 9 attenuates ischemic acute kidney injury.Kidney international · 2020Article
- P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- The Yin and Yang of Alarmins in Regulation of Acute Kidney Injury.Frontiers in medicine · 2020Review
- Mechanisms and therapeutic targets of ischemic acute kidney injury.Kidney research and clinical practice · 2019Review
- Extracellular DNA traps in inflammation, injury and healing.Nature reviews. Nephrology · 2019Review
- Peptidyl arginine deiminase-4 exacerbates ischemic AKI by finding NEMO.American journal of physiology. Renal physiology · 2019Article
- Epithelial and Endothelial Pannexin1 Channels Mediate AKI.Journal of the American Society of Nephrology : JASN · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We previously demonstrated that renal tubular peptidylarginine deiminase-4 (PAD4) is induced after ischemia-reperfusion (IR) injury and this induction of PAD4 exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular inflammation and neutrophil infiltration. However, the mechanisms of renal tubular PAD4 induction after IR remain unknown. Here, we tested the hypothesis that ATP, a proinflammatory danger-associated molecular pattern (DAMP) ligand released from necrotic cells after IR injury, induces renal tubular PAD4 and exacerbates ischemic AKI via P2 purinergic receptor activation. ATP as well as ATPγS (a nonmetabolizable ATP analog) induced PAD4 mRNA, protein, and activity in human and mouse renal proximal tubule cells. Supporting the hypothesis that ATP induces renal tubular PAD4 via P2X7 receptor activation, A804598 (a selective P2X7 receptor antagonist) blocked the ATP-mediated induction of renal tubular PAD4 whereas BzATP (a selective P2X7 receptor agonist) mimicked the effects of ATP by inducing renal tubular PAD4 expression and activity. Moreover, ATP-mediated calcium influx in renal proximal tubule cells was blocked by A804598 and was mimicked by BzATP. P2X7 activation by BzATP also induced PAD4 expression and activity in mouse kidney in vivo. Finally, supporting a critical role for PAD4 in P2X7-mediated exacerbation of renal injury, BzATP exacerbated ischemic AKI in PAD4 wild-type mice but not in PAD4-deficient mice. Taken together, our studies show that ATP induces renal tubular PAD4 via P2X7 receptor activation to exacerbate renal tubular inflammation and injury after IR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.