ArticleJournal of hepatology2013
Endoplasmic reticulum stress induces fibrogenic activity in hepatic stellate cells through autophagy.
Article in Journal of hepatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 227 citations in OpenAlex.
- A Hepatocyte-to-Stellate Cell Axis Couples Alternate-Day Fasting to Liver Fibrosis Resolution via ATG7 S-Nitrosylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The PERK-GADD45A axis is a key driver of hepatic stellate cell activation.Hepatology communications · 2026Article
- FAM134B controls collagen I dynamics in hepatic stellate cell-driven fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- From metabolic antagonism to homeostatic restoration: rewiring hepatic stellate cell bioenergetics for liver fibrosis reversal.Frontiers in medicine · 2026Review
- Autophagy in the liver.Autophagy reports · 2026Review
- Cell-specific roles of autophagy in liver fibrosis: implications for targeted pharmacotherapy.Annals of medicine · 2025Review
- Arctigenin Attenuates Hepatic Stellate Cell Activation via Endoplasmic Reticulum-Associated Degradation (ERAD)-Mediated Restoration of Lipid Homeostasis.Journal of agricultural and food chemistry · 2025Article
- Enolase and 16.5-kDa Tegument-Associated Protein inJournal of extracellular biology · 2025Article
- Hepatotoxicity of titanium dioxide nanoparticles.Journal of applied toxicology : JAT · 2025Review
- Biomimetic mesenchymal stem cell membrane-coated nanoparticle delivery of MKP5 inhibits hepatic fibrosis through the IRE/XBP1 pathway.Journal of nanobiotechnology · 2024Article
- Lipids associated with autophagy: mechanisms and therapeutic targets.Cell death discovery · 2024Review
- The effects of TGF-β-induced activation and starvation of vitamin A and palmitic acid on human stem cell-derived hepatic stellate cells.Stem cell research & therapy · 2024Article
- Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells.International journal of molecular sciences · 2024Review
- Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease.Autophagy · 2024Review
- Associations of dietary sources of antioxidant intake and NAFLD: NHANES 2017-2020 and Mendelian randomization.Frontiers in nutrition · 2024Article
- Redox Biology and Liver Fibrosis.International journal of molecular sciences · 2023Review
- Autophagy modulates physiologic and adaptive response in the liver.Liver research (Beijing, China) · 2023Review
- Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH).Science translational medicine · 2023Review
- Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- Stress and Liver Fibrogenesis: Understanding the Role and Regulation of Stress Response Pathways in Hepatic Stellate Cells.The American journal of pathology · 2023Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsMetabolic stress during liver injury enhances autophagy and provokes stellate cell activation, with secretion of scar matrix. Conditions that augment protein synthesis increase demands on the endoplasmic reticulum (ER) folding capacity and trigger the unfolded protein response (UPR) to cope with resulting ER stress. Generation of reactive oxygen species (ROS) is a common feature of hepatic fibrogenesis, and crosstalk between oxidant stress and ER stress has been proposed. The aim of our study was to determine the impact of oxidant and ER stress on stellate cell activation.
methodsOxidant stress was induced in hepatic stellate cells using H2O2 in culture or by ethanol feeding in vivo, and the UPR was analyzed. Because the branch of the UPR mainly affected was IREα, we blocked this pathway in stellate cells and analyzed the fibrogenic response, together with autophagy and downstream MAPK signaling. The Nrf2 antioxidant response was also evaluated in stellate cells under oxidant stress conditions.
resultsH2O2 treatment in culture or ethanol feeding in vivo increased the UPR based on splicing of XBP1 mRNA, which triggered autophagy. The Nrf2-mediated antioxidant response, as measured by qRT-PCR of its target genes was also induced under ER stress conditions. Conversely, blockade of the IRE1α pathway in stellate cells significantly decreased both their activation and autophagic activity in a p38 MAPK-dependent manner, leading to a reduced fibrogenic response.
conclusionsThese data implicate mechanisms underlying protein folding quality control in regulating the fibrogenic response in hepatic stellate cells.
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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.