ArticleNature communications2025
Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- Integrated Stress Response and Drug-Induced Acute Kidney Injury: Involvement of Activating ATF4-STAT1-GBP2 Signaling.Journal of the American Society of Nephrology : JASN · 2026Article
- The PERK-GADD45A axis is a key driver of hepatic stellate cell activation.Hepatology communications · 2026Article
- High-Intensity Interval Training Attenuates Hepatic Fibrosis by Remodeling Lactate Metabolism in MASLD.Metabolites · 2026Article
- Unraveling the HGF/MET axis in Mallory-Denk body pathogenesis associated with liver fibrosis through single-cell transcriptomics.Signal transduction and targeted therapy · 2026Article
- Pirfenidone Sensitizes Hepatic Stellate Cells to Ferroptosis by Reprogramming Glutamine and Serine Metabolism for GSH Depletion.Antioxidants (Basel, Switzerland) · 2026Article
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- Targeting FGG alleviates cholestatic fibrosis by inhibiting hepatic stellate cell activation and regulating macrophage homeostasis.Journal of nanobiotechnology · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- M2 macrophage-derived apoptotic vesicles alleviate liver fibrosis via miR-1224-5p-mediated inhibition of the SP1/TGF-β pathway in hepatic stellate cells.Journal of nanobiotechnology · 2026Article
- Article
- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1.Hepatology (Baltimore, Md.) · 2026Article
- UNC93B1 promotes pancreatic cancer progression through modulation of cGAS-STING signaling.Frontiers in immunology · 2026Article
- Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis.International journal of nanomedicine · 2026Review
- Title: Resveratrol ameliorates liver fibrosis by inhibiting ATF4 to regulate glutamine metabolism in hepatic stellate cells.Archives of pharmacal research · 2025Article
- Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation.Science advances · 2025Article
- Synergistic therapeutic strategies for metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus: molecular insights and clinical advances.Frontiers in endocrinology · 2025Review
- Applications of AI to single-cell and spatial transcriptomics: current state-of-the-art and challenges.Frontiers in bioinformatics · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions. HSC-specific depletion of ATF4 suppresses liver fibrosis in vivo. Mechanistically, TGFβ resets ATF4 to orchestrate a unique enhancer program for the transcriptional activation of pro-fibrotic EMT genes. Analysis of human data confirms a strong correlation between HSC ATF4 expression and liver fibrosis progression. Importantly, a small molecule inhibitor targeting ATF4 translation effectively mitigates liver fibrosis. Together, our findings identify a mechanism promoting liver fibrosis and reveal new opportunities for treating this otherwise non-targetable disease.
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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 Socratic graph.