ArticleThe Journal of clinical investigation2014
TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Pooled it
- N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial.Critical care (London, England) · 2016Trial
- Pathophysiological significance of the TRPM2 ion channel as a potential target in cancer, neurological disorders, and ischemia/reperfusion injury.Pharmacological research · 2026Review
- Neuroimmune Regulation by TRPM2 Channels.Cells · 2026Review
- Dexmedetomidine protects against ischemia and reperfusion-induced kidney injury in rats by inhibiting the expression of TRPM2 and TRPA1 channels.Iranian journal of basic medical sciences · 2026Article
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- High-Fat-Diet-Induced Kidney Injury in Rats: The Role of Tart Cherry Supplementation.Antioxidants (Basel, Switzerland) · 2025Article
- Protective effects of tasimelteon on kidney injury in a traumatic brain injury rat model: a histopathological and immunohistochemical study.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Article
- ROS-Activated TRPM2 Channel: Calcium Homeostasis in Cardiovascular/renal System and Speculation in Cardiorenal Syndrome.Cardiovascular drugs and therapy · 2025Review
- [Advances in the development of transient receptor potential melastatin 2 channel inhibitors].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- The Effect of Selenium Against Cadmium-Induced Nephrotoxicity in Rats: The Role of the TRPM2 Channel.Toxics · 2025Article
- TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway.Molecular and cellular biochemistry · 2024Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- TRPM channels in health and disease.Nature reviews. Nephrology · 2024Review
- Membrane Dynamics and Cation Handling in Ferroptosis.Physiology (Bethesda, Md.) · 2024Review
- The Combination of 5-FU and Resveratrol Can Suppress the Growth of Glioblastoma Cells Through Downregulation of TRPM2 and β-Catenin.Journal of molecular neuroscience : MN · 2024Article
- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- The Role of Oxidative Stress in Kidney Injury.Antioxidants (Basel, Switzerland) · 2023Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Ischemia is a leading cause of acute kidney injury. Kidney ischemia is associated with loss of cellular ion homeostasis; however, the pathways that underlie ion homeostasis dysfunction are poorly understood. Here, we evaluated the nonselective cation channel transient receptor potential melastatin 2 (TRPM2) in a murine model of kidney ischemia/reperfusion (I/R) injury. TRPM2-deficient mice were resistant to ischemic injury, as reflected by improved kidney function, reduced histologic damage, suppression of proapoptotic pathways, and reduced inflammation. Moreover, pharmacologic TRPM2 inhibition was also protective against I/R injury. TRPM2 was localized mainly in kidney proximal tubule epithelial cells, and studies in chimeric mice indicated that the effects of TRPM2 are due to expression in parenchymal cells rather than hematopoietic cells. TRPM2-deficient mice had less oxidative stress and lower levels of NADPH oxidase activity after ischemia. While RAC1 is a component of the NADPH oxidase complex, its relation to TRPM2 and kidney ischemic injury is unknown. Following kidney ischemia, TRPM2 promoted RAC1 activation, with active RAC1 physically interacting with TRPM2 and increasing TRPM2 expression at the cell membrane. Finally, inhibition of RAC1 reduced oxidant stress and ischemic injury in vivo. These results demonstrate that TRPM2-dependent RAC1 activation increases oxidant stress and suggest that therapeutic approaches targeting TRPM2 and/or RAC1 may be effective in reducing ischemic kidney injury.
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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.