ArticleJournal of hepatology2020
Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis.
Article in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
158 citing papers in PubMed.
- p21-activated kinase 4 drives hepatic stellate cell activation and liver fibrosis through the phosphorylation of YAP at T428.Signal transduction and targeted therapy · 2026Article
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy.Aging cell · 2026Article
- The P2X4-P2X7 purinergic axis in alcohol-related liver disease: from fibrogenesis to immunotherapy resistance.Purinergic signalling · 2026Review
- mTOR-driven integrin β4-enriched extracellular vesicles from lenvatinib-resistant hepatocellular carcinoma fuel lung metastasis via fibroblast-niche formation.Signal transduction and targeted therapy · 2026Article
- CCT7 Regulates TRAF6-Mediated Autophagy to Promote Posttraumatic Joint Contracture.Journal of cellular and molecular medicine · 2026Article
- Preclinical efficacy and safety evaluation of human embryonic stem cell-derived functional hepatocytes for a clinical trial in acute liver failure.Stem cell research & therapy · 2026Article
- Integrative study revealsWorld journal of gastroenterology · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Autophagy-mediated Kupffer cell polarization in liver cirrhosis reversal: Mechanistic insights and therapeutic strategies.Liver research (Beijing, China) · 2026Review
- P7C3 alleviates hepatic fibrosis via targeting eIF4A1-mediated protein translation and autophagy in hepatic stellate cells.Archives of pharmacal research · 2026Article
- Orphan drug uttroside B impedes MASH progression and HCC development in experimental models.JHEP reports : innovation in hepatology · 2026Article
- Autocrine Netrin-1 Signaling in Hepatic Stellate Cells Drives Liver Fibrosis and Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Platelet-mediated progression of fatty liver disease in metabolic dysfunction-associated steatohepatitis: a pathophysiological review.Frontiers in medicine · 2026Review
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- 80 years of extracellular vesicles: from discovery to clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Recent Advances in the Study of Traditional Chinese Medicine in Reversing Hepatic Fibrosis Through the Regulation of Hepatic Stellate Cells Apoptosis Pathways.Drug design, development and therapy · 2026Review
- Loganin Ameliorates Cholestatic Liver Fibrosis by Inhibiting Hepatic Stellate Cell Autophagy and Activation Through EGFR Signaling.Mediators of inflammation · 2026Article
- Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice?International journal of molecular sciences · 2025Review
- Senkyunolide A ameliorates cholestatic liver fibrosis by controlling CLCC1-mediated endoplasmic reticulum CaActa pharmacologica Sinica · 2025Article
98 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
10 authors.
Funding
Abstract
BACKGROUND &
aimsAutophagy plays a crucial role in hepatic homeostasis and its deregulation has been associated with chronic liver disease. However, the effect of autophagy on the release of fibrogenic extracellular vesicles (EVs) by platelet-derived growth factor (PDGF)-stimulated hepatic stellate cells (HSCs) remains unknown. Herein, we aimed to elucidate the role of autophagy, specifically relating to fibrogenic EV release, in fibrosis.
methodsIn vitro experiments were conducted in primary human and murine HSCs as well as LX2 cells. Small EVs were purified by differential ultracentrifugation. Carbon tetrachloride (CCl
resultsIn vitro, PDGF and its downstream molecule SHP2 (Src homology 2-containing protein tyrosine phosphatase 2) inhibited autophagy and increased HSC-derived EV release. We used this PDGF/SHP2 model to further investigate how autophagy affects fibrogenic EV release. RNA sequencing identified an mTOR (mammalian target of rapamycin) signaling molecule that was regulated by SHP2 and PDGF. Disruption of mTOR signaling abolished PDGF-dependent EV release. Activation of mTOR signaling induced the release of multivesicular body-derived exosomes (by inhibiting autophagy) and microvesicles (by activating ROCK1 signaling). These mTOR-dependent EVs promoted in vitro HSC migration. To assess the importance of this mechanism in vivo, SHP2 was selectively deleted in HSCs, which attenuated CCl
conclusionThese results demonstrate that autophagy in HSCs attenuates liver fibrosis by inhibiting the release of fibrogenic EVs. LAY SUMMARY: During liver fibrosis and cirrhosis, activated hepatic stellate cells (HSCs) are the key cell type responsible for fibrotic tissue deposition. Recently, we demonstrated that activated HSCs release nano-sized vesicles enriched with fibrogenic proteins. In the current study, we unveil the mechanism by which these fibrogenic vesicles are released, moving a step closer to the long-term goal of therapeutically targeting this process.
Indexed as
Identifiers
What OpenQuestion holds
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.