ArticleCell death & disease2018
Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- Trem1 regulates neutrophil metabolism and recruitment in lung ischemia-reperfusion injury.Redox biology · 2026Article
- The dual role of ATF3 in myocardial repair through macrophage regulation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Hepatic activating transcription factor 3 protects against systemic inflammation by attenuating lipotoxicity.Metabolism open · 2025Article
- Copy Number Gains of VPS72 Drive De Novo Lipogenesis and Hepatocarcinogenesis via ATF3/mTORC1/SREBP1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Insights into the Molecular Mechanisms of Bushen Huoxue Decoction in Breast CancerCurrent computer-aided drug design · 2025Article
- Loss of adipose ATF3 promotes adipose tissue lipolysis and the development of MASH.Communications biology · 2024Article
- Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells.Apoptosis : an international journal on programmed cell death · 2024Article
- Protective hepatocyte signals restrain liver fibrosis in metabolic dysfunction-associated steatohepatitis.The Journal of clinical investigation · 2024Article
- Loss of macrophage TSC1 exacerbates sterile inflammatory liver injury through inhibiting the AKT/MST1/NRF2 signaling pathway.Cell death & disease · 2024Article
- Transaldolase inhibits CD36 expression by modulating glutathione-p38 signaling, exerting protective effects against macrophage foam cell formation.Acta biochimica et biophysica Sinica · 2023Article
- The Role of Activating Transcription Factor 3 in Metformin's Alleviation of Gastrointestinal Injury Induced by Restraint Stress in Mice.International journal of molecular sciences · 2023Article
- Activating transcription factor 3, glucolipid metabolism, and metabolic diseases.Journal of molecular cell biology · 2023Article
- Multiple Beneficial Effects of Aloesone fromMolecules (Basel, Switzerland) · 2023Article
- Therapeutically targeting essential metabolites to improve immunometabolism manipulation after liver transplantation for hepatocellular carcinoma.Frontiers in immunology · 2023Review
- The hepatic integrated stress response suppresses the somatotroph axis to control liver damage in nonalcoholic fatty liver disease.Cell reports · 2022Article
- ATF3 in atherosclerosis: a controversial transcription factor.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Notch-activated mesenchymal stromal/stem cells enhance the protective effect against acetaminophen-induced acute liver injury by activating AMPK/SIRT1 pathway.Stem cell research & therapy · 2022Article
- Hepatic Ischemia-reperfusion Injury in Mice was Alleviated by Rac1 Inhibition - More Than Just ROS-inhibition.Journal of clinical and translational hepatology · 2022Article
- Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis regulates immune responses in a liver ischemia/reperfusion injury (IRI) model. Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular apoptosis, and the upregulation of pro-inflammatory mediators. ATF3 deficiency promoted mTOR and p70S6K phosphorylation, activated high mobility group box 1 (HMGB1) and TLR4, inhibited prolyl-hydroxylase 1 (PHD1), and increased HIF-1α activity, leading to Foxp3 downregulation and RORγt and IL-17A upregulation in IRI livers. Blocking mTOR or p70S6K in ATF3 knockout (KO) mice or bone marrow-derived macrophages (BMMs) downregulated HMGB1, TLR4, and HIF-1α and upregulated PHD1, increasing Foxp3 and decreasing IL-17A levels in vitro. Silencing of HIF-1α in ATF3 KO mice ameliorated IRI-induced liver damage in parallel with the downregulation of IL-17A in ATF3-deficient mice. These findings demonstrated that ATF3 deficiency activated mTOR/p70S6K/HIF-1α signaling, which was crucial for the modulation of TLR4-driven inflammatory responses and T cell development. The present study provides potential therapeutic targets for the treatment of liver IRI followed by liver transplantation.
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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.