ArticleJournal of translational medicine2024
Blockade of the mitochondrial DNA release ameliorates hepatic ischemia-reperfusion injury through avoiding the activation of cGAS-Sting pathway.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Toll-like receptor 9-overexpressing red blood cell biomimetic microbubbles adsorb cell-free DNA to relieve steatotic liver ischemia-reperfusion injury.Materials today. Bio · 2026Article
- Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation.Journal of hematology & oncology · 2026Article
- The diversity of STING in regulating immune cell function and its role in liver diseases: from bench to bedside.Cell & bioscience · 2026Review
- A dual-responsive CO-releasing nanogel ameliorates retinal ischemia-reperfusion injury by restoring mitochondrial homeostasis and attenuating cGAS-STING pathway activation.Materials today. Bio · 2026Article
- Targeting VPS4 elicits STING-driven anti-tumor immunity to suppress rhabdomyosarcoma growth.Oncogene · 2026Article
- Mechano-metabolic feedback connects tissue fluidity to mitochondrial DNA-dependent immunity in breast cancer.Nature communications · 2026Article
- Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies.Journal of translational medicine · 2026Review
- Protective effect of ischemic preconditioning against hepatic ischemia-reperfusion injury and associated remote organ damage.World journal of gastrointestinal surgery · 2026Review
- Damage-associated molecular patterns in hepatic ischemia-reperfusion injury: spatiotemporal signatures, biomarker potential, and clinical translation.Frontiers in immunology · 2026Review
- Deoxyguanosine kinase deficiency couples purine metabolism to innate immune activation and lipid accumulation in hepatocytes.Frontiers in immunology · 2026Article
- Mitochondrial homeostasis and aging: the mtDNA-cGAS-STING axis.Frontiers in immunology · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- Bimodal regulation and precision therapy of neutrophil extracellular traps in liver ischemia-reperfusion injury: recent advances.Frontiers in immunology · 2026Review
- Mitochondrial dysfunction in immune cells during the perioperative period: mechanisms, emerging therapeutic strategies, and implications for multi-organ protection.Frontiers in immunology · 2026Review
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- [Research progress on the cGAS-STING signaling pathway in immune-mediated inflammatory diseases in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Dimethyl fumarate alleviate hepatic ischemia-reperfusion injury through suppressing cGAS-STING signaling.MedComm · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundLiver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated.
methodsMouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models.
resultsOur research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization.
conclusionsThe results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury.
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