ArticleInternational journal of molecular medicine2017
Autophagy mediated by endoplasmic reticulum stress enhances the caffeine-induced apoptosis of hepatic stellate cells.
Article in International journal of molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Prolonged high-dose prenatal caffeine exposure induces organ-specific developmental toxicity: renal p53 downregulation and hepatic caspase-3 upregulation in neonatal mice, supported with in silico studies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Leptin-dependent fat accumulation triggers autophagy in metabolic dysfunction-associated steatohepatitis model.Translational gastroenterology and hepatology · 2026Article
- Effects of caffeine supplementation on lipid profile and handgrip strength in cirrhotic patients: a randomized, placebo- controlled, clinical trial.BMC nutrition · 2025Article
- Knockdown of circ_0044226 promotes endoplasmic reticulum stress-mediated autophagy and apoptosis in hepatic stellate cells via miR-4677-3p/SEC61G axis.Journal of bioenergetics and biomembranes · 2024Article
- Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease.Autophagy · 2024Review
- Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- Article
- Review
- Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Implication of autophagy in the antifibrogenic effect of Rilpivirine: when more is less.Cell death & disease · 2022Article
- Heparanase Inhibition Prevents Liver Steatosis in EJournal of clinical medicine · 2022Article
- Portulaca oleracea L. Extract Ameliorates Intestinal Inflammation by Regulating Endoplasmic Reticulum Stress and Autophagy.Molecular nutrition & food research · 2022Article
- Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model.Nutrients · 2021Article
- Review
- Caffeine Induces Autophagy and Apoptosis in Auditory Hair CellsFrontiers in cell and developmental biology · 2021Article
- Article
- [Endoplasmic reticulum stress enhances tumor necrosis factor-Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Caffeine and Parkinson's Disease: Multiple Benefits and Emerging Mechanisms.Frontiers in neuroscience · 2020Review
- Kupffer Cell-Derived TNF-BioMed research international · 2020Article
- High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver.Scientific reports · 2019Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caffeine has been identified to have beneficial effects against chronic liver diseases, particularly liver fibrosis. Many studies have reported that caffeine ameliorates liver fibrosis by directly inducing hepatic stellate cell (HSC) apoptosis; however, the molecular mechanisms involved in this process remain unclear. The presents study aimed to detect the underlying mechanisms by which caffeine mediates HSC apoptosis and eliminates activated HSCs. For this purpose, the LX-2 cell line was applied in this study and the cells were exposed to various concentrations of caffeine for the indicated times. The effects of caffeine on cell viability and apoptosis were assessed by Cell Counting Kit-8 assay and flow cytometry, respectively. Autophagy and endoplasmic reticulum (ER) stress were explored by morphological assessment and western blotting. In the present study, caffeine was found to inhibit the viability and increase the apoptosis of the LX-2 cells in dose- and time-dependent manners. ER stress was stimulated by caffeine as demonstrated by increased levels of GRP78/Bip, CHOP and inositol‑requiring enzyme 1 (IRE1)-α as well as many enlarged ERs detected by electron microscopy. Caffeine induced autophagy as shown by increased p62 and LC3Ⅱ accumulation and the number of GFP/RFP-LC3 puncta and autophagosomes/autolysosomes. Moreover, IRE1-α knockdown decreased the level of autophagic flux, and inhibition of autophagy protected LX-2 cells from apoptotic death. In conclusion, our study showed that the caffeine-enhanced autophagic flux in HSCs was stimulated by ER stress via the IRE1-α signaling pathway, which further weakened HSC viability via the induction of apoptosis. These findings provide new insight into the mechanism of caffeine's anti-fibrotic effects.
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