ArticleAmerican journal of physiology. Renal physiology2018
Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins.
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 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- The Role of Macrophage M1/M2 Polarization Imbalance in the Pathogenesis of Immune Associated Diffuse Alveolar Hemorrhage: Evidence From the Study of Human Clinical Specimens.Pediatric pulmonology · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Article
- Endogenous Ligands of TLR4 in Microglia: Potential Targets for Related Neurological Diseases.Current drug targets · 2024Review
- Targeting heme in sickle cell disease: new perspectives on priapism treatment.Frontiers in physiology · 2024Review
- Neuregulin-1 attenuates hemolysis- and ischemia induced-cerebrovascular inflammation associated with sickle cell disease.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2023Article
- Heme Proteins and Kidney Injury: Beyond Rhabdomyolysis.Kidney360 · 2022Review
- Review
- Sickle cell nephropathy: insights into the pediatric population.Pediatric nephrology (Berlin, Germany) · 2022Review
- Augmenter of Liver Regeneration (ALR) Protects Kidney from Ischemia/Reperfusion (I/R) Injury via Regulation of TLR4/MAPK Signaling Pathway.Journal of immunology research · 2022Article
- Heme Oxygenase-1 may Mediate Early Inflammatory Response of Intracerebral Hemorrhage through Toll-like Receptor 4 Signaling Pathway.Current neurovascular research · 2022Article
- Heme induces significant neutrophil adhesion in vitro via an NFκB and reactive oxygen species-dependent pathway.Molecular and cellular biochemistry · 2021Article
- Potential therapeutic effects of Nrf2 activators on intracranial hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders.International journal of molecular sciences · 2021Review
- Red yeast rice (Monascus purpureus) supplements: Case series assessment of spontaneously reported cases to The Netherlands Pharmacovigilance Centre Lareb.British journal of clinical pharmacology · 2021Article
- Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation.Kidney international · 2021Article
- Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases.International journal of molecular sciences · 2021Review
- Toll-Like Receptors in Acute Kidney Injury.International journal of molecular sciences · 2021Review
- High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease.Journal of thrombosis and haemostasis : JTH · 2020Article
- Endothelial TLR4 Expression Mediates Vaso-Occlusive Crisis in Sickle Cell Disease.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Destabilized heme proteins release heme, and free heme is toxic. Heme is now recognized as an agonist for the Toll-like receptor-4 (TLR4) receptor. This study examined whether the TLR4 receptor mediates the nephrotoxicity of heme, specifically, the effects of heme on renal blood flow and inflammatory responses. We blocked TLR4 signaling by the specific antagonist TAK-242. Intravenous administration of heme to mice promptly reduced renal blood flow, an effect attenuated by TAK-242. In vitro, TAK-242 reduced heme-elicited activation of NF-κB and its downstream gene monocyte chemoattractant protein-1(MCP-1); in contrast, TAK-242 failed to reduce heme-induced activation of the anti-inflammatory transcription factor Nrf2 and its downstream gene heme oxygenase-1 (HO-1). TAK-242 did not reduce heme-induced renal MCP-1 upregulation in vivo. TAK-242 did not reduce dysfunction and histological injury in the glycerol model of heme protein-induced acute kidney injury (AKI), findings corroborated by studies in TLR4
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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.