ArticleScience advances2024
IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Molecular mechanisms and therapeutic strategies of cGAS-STING pathway in liver disease: the quest continues.Frontiers in immunology · 2025Pooled it
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- PLXDC2 siRNA-Mediated Intervention Attenuates Microglial Senescence Through cGAS-STING Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Context-dependent duality of senescent cells in liver fibrosis.Liver research (Beijing, China) · 2026Review
- Genome-wide association study of sarcopenia index reveals sex-stratified genetic architecture.Biology of sex differences · 2026Article
- Combining Radiation-Treated Tumor Vaccines With Mn-MOF Nanoadjuvants to Amplify Radiation Induced Anti-Tumor Immune Responses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Oncogenic EGFR rewires STING-TBK1 signalosomes to license DNA damage tolerance in NSCLC.The EMBO journal · 2026Article
- cGAS-STING signaling in aging and age-related diseases: therapeutic promise and precaution.Archives of pharmacal research · 2026Review
- [Mechanisms of cGAS-STING-mediated chronic inflammation and targeted interventions in brain aging].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Review
- Targeting the cGAS-STING pathway alleviates neuroinflammation and cognitive impairment induced by chronic infection of Toxoplasma gondii.Journal of neuroinflammation · 2026Article
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.Investigative ophthalmology & visual science · 2026Review
- Mitochondrial Protection by Trifolirhizin Alleviates Primary Sjögren's Syndrome and Liver Injury via Coordinated Suppression of the ROS/cGAS-STING Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Non-transcriptional activity of IRF3 promotes liver fibrosis and stress granule assembly via a dsRNA-TLR3-dependent pathway in hepatic stellate cells.Hepatology (Baltimore, Md.) · 2026Article
- Facilitated DNA damage repair as an emerging therapeutic strategy for inflammatory and fibrotic diseases.RSC chemical biology · 2026Review
- CRISPLD2 protects against liver inflammation and fibrosis via GRP78 to repress HMGB1/TLR4 axis-mediated STING palmitoylation.Hepatology communications · 2026Article
10 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
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator. The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within various murine models, pushing activated HSCs toward senescence. Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.
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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.