ArticleJournal of gastroenterology2023
Mitochondrial stress induces hepatic stellate cell activation in response to the ATF4/TRIB3 pathway stimulation.
Article in Journal of gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Pirfenidone Sensitizes Hepatic Stellate Cells to Ferroptosis by Reprogramming Glutamine and Serine Metabolism for GSH Depletion.Antioxidants (Basel, Switzerland) · 2026Article
- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- Furin inhibits HSCs activation and ameliorates liver fibrosis by regulating PTEN-L/PINK1/parkin mediated mitophagy in mouse.FASEB bioAdvances · 2025Article
- TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells.Nature communications · 2025Article
- Multiorgan crosstalk in MASLD/MASH: from hepatic pathogenesis to systemic complications.Frontiers in endocrinology · 2025Review
- Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.Heliyon · 2024Article
- Stress and Liver Fibrogenesis: Understanding the Role and Regulation of Stress Response Pathways in Hepatic Stellate Cells.The American journal of pathology · 2023Review
- TRIB3, as a robust prognostic biomarker for HNSC, is associated with poor immune infiltration and cancer cell immune evasion.Frontiers in immunology · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe activation of hepatic stellate cells (HSCs) is the key step in the pathogenesis of liver fibrosis, which directly leads to fibrotic pathological changes in the hepatic tissue. Mitochondrial stress exacerbates inflammatory diseases by inducing pathogenic shifts in normal cells. However, the role of mitochondrial stress in HSC activation remains to be elucidated.
methodsWe analyzed the effect of mitochondrial stress on HSC activation. An in vivo hepatic fibrosis model was established by intraperitoneal injection of 40% carbon tetrachloride (CCl
resultsTranscriptional activator 4 (ATF4) is highly expressed in fibrotic liver tissue samples and activated HSCs. We found that AAV8-shRNA-Atf4 alleviated liver fibrosis in rats. ATF4 promoted the activation of HSCs, which was induced by mitochondrial stress. The mechanisms involved ATF4 binding to a specific region of the tribble homologue 3 (TRIB3) promoter. Further, TRIB3 promoted HSCs activation mediated by mitochondrial stress.
conclusionsATF4 induces mitochondrial stress by upregulating TRIB3, leading to the activation of HSCs. Therefore, the inhibition of ATF4 during mitochondrial stress may be a promising therapeutic target for liver fibrosis.
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