ArticleJournal of the American Society of Nephrology : JASN2016
Role of Mitochondrial DNA in Septic AKI via Toll-Like Receptor 9.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Pooled it
- Nucleic acid sensing pathways in kidney disease development.Nature reviews. Nephrology · 2026Review
- Lipidomic profiling reveals medium-chain acylcarnitines alterations as metabolic signatures in IgA nephropathy.BMC nephrology · 2026Article
- Cell-free mitochondrial DNA (cf-mtDNA) in human body fluids: molecular characteristics, release mechanisms, and clinical translation-an updated review.Frontiers in molecular biosciences · 2026Review
- Mitophagy in kidney and lung epithelial cells: molecular mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Review
- Kidney mitochondrial DNA contributes to systemic IL-6 release in sepsis-associated acute kidney injury.JCI insight · 2025Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy.Molecular biomedicine · 2025Review
- Beyond the Blood Cell: The Emerging Role of Cell-Free DNA in Transfusion Medicine.Journal of hematology · 2025Review
- Toll like receptor 2 mediated exacerbation of sepsis associated acute kidney injury by renal congestion in mice.Scientific reports · 2025Article
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- The Role of Mitochondrial Dysfunction in Sepsis-Associated Acute Kidney Injury: A Narrative Review.Drug design, development and therapy · 2025Review
- Cell-free mitochondrial DNA as a pro-inflammatory agent in blood circulation: mechanisms, therapeutic implications, and clinical challenges in immune dysregulation.Frontiers in immunology · 2025Review
- Plasma total and donor-derived cell-free DNA predict survival in kidney transplant recipients.Frontiers in transplantation · 2025Article
- Mitochondrial dysfunction in sepsis: mechanisms and therapeutic perspectives.Critical care (London, England) · 2024Review
- Alkaline phosphatase treatment of acute kidney injury-an update.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Higher Molecular Injury at Diagnosis of Acute Cellular Rejection Increases the Risk of Lung Allograft Failure: A Clinical Trial.American journal of respiratory and critical care medicine · 2024Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 9 (TLR9) contributes to the development of polymicrobial septic AKI. However, the mechanisms that activate the TLR9 pathway and cause kidney injury during sepsis remain unknown. To determine the role of mitochondrial DNA (mtDNA) in TLR9-associated septic AKI, we established a cecal ligation and puncture (CLP) model of sepsis in wild-type (WT) and Tlr9-knockout (Tlr9KO) mice. We evaluated systemic circulation and peritoneal cavity dynamics and immune response and tubular mitochondrial dysfunction to determine upstream and downstream effects on the TLR9 pathway, respectively. CLP increased mtDNA levels in the plasma and peritoneal cavity of WT and Tlr9KO mice in the early phase, but the increase in the peritoneal cavity was significantly higher in Tlr9KO mice than in WT mice. Concomitantly, leukocyte migration to the peritoneal cavity increased, and plasma cytokine production and splenic apoptosis decreased in Tlr9KO mice compared with WT mice. Furthermore, CLP-generated renal mitochondrial oxidative stress and mitochondrial vacuolization in the proximal tubules in the early phase were reversed in Tlr9KO mice. To elucidate the effects of mtDNA on immune response and kidney injury, we intravenously injected mice with mitochondrial debris (MTD), including substantial amounts of mtDNA. MTD caused an immune response similar to that induced by CLP, including upregulated levels of plasma IL-12, splenic apoptosis, and mitochondrial injury, but this effect was attenuated by Tlr9KO. Moreover, MTD-induced renal mitochondrial injury was abolished by DNase pretreatment. These findings suggest that mtDNA activates TLR9 and contributes to cytokine production, splenic apoptosis, and kidney injury during polymicrobial sepsis.
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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.