ArticleNature communications2021
Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 121 citations in OpenAlex.
- Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential.Biomolecules · 2026Review
- A bioengineered platform reveals progressive impairment of skeletal muscles by metabolic dysfunction-associated steatotic liver disease-derived factors.Disease models & mechanisms · 2026Article
- Hepatocyte CD146 and soluble CD146 promote hepatic stellate cell activation via the integrin αvβ1-p38 MAPK signaling axis to drive liver fibrosis.Cellular and molecular life sciences : CMLS · 2026Article
- An LSEC-focused computational drug repurposing platform for liver fibrosis: Identification of vorinostat and other LSEC-protective candidates.bioRxiv : the preprint server for biology · 2026Article
- Small extracellular vesicles derived from lipotoxic hepatocytes transport FASN to promote hepatic stellate cell activation.Hepatology international · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Hepatocyte-hepatic stellate cell interactions in liver fibrosis: Mechanisms and therapeutic implications.Hepatology communications · 2026Review
- The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress.Antioxidants (Basel, Switzerland) · 2026Review
- Metabolic reprogramming in cardiac fibrosis: mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Hepatic Stellate Cell-derived IL-11 Exacerbates Liver Fibrosis via Interplay between HSCs and Macrophages.International journal of biological sciences · 2026Article
- The role of IL-11 in chronic diseases.Frontiers in immunology · 2026Review
- Article
- Shugan Xiaozhi Decoction attenuates nonalcoholic steatohepatitis by modulating oxidative stress and AMPK pathway.BMC complementary medicine and therapies · 2025Article
- Linc01271 promotes lipid synthesis and MASLD/MASH progression via miR-149-3p/RAB35 axis.Cellular and molecular life sciences : CMLS · 2025Article
- MCM7 promotes liver fibrosis by transcriptionally regulating IL11 via the SHCBP1-RACGAP1-STAT3 axis.Cell death & disease · 2025Article
- Hepatic stellate cell-specific Kcnma1 deletion mitigates metabolic dysfunction-associated steatotic liver disease progression via upregulating Amphiregulin secretion.Molecular metabolism · 2025Article
- ESRRA (estrogen related receptor, alpha) induces ribosomal protein RPLP1-mediated adaptive hepatic translation during prolonged starvation.Autophagy · 2025Article
- Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C.Clinical and molecular hepatology · 2025Article
- Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Consumption of Endogenous Caspase-3 Activates Molecular Theranostic Nanoplatform against Inflammation-Induced Profibrotic Positive Feedback in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
Abstract
IL11 is important for fibrosis in non-alcoholic steatohepatitis (NASH) but its role beyond the stroma in liver disease is unclear. Here, we investigate the role of IL11 in hepatocyte lipotoxicity. Hepatocytes highly express IL11RA and secrete IL11 in response to lipid loading. Autocrine IL11 activity causes hepatocyte death through NOX4-derived ROS, activation of ERK, JNK and caspase-3, impaired mitochondrial function and reduced fatty acid oxidation. Paracrine IL11 activity stimulates hepatic stellate cells and causes fibrosis. In mouse models of NASH, hepatocyte-specific deletion of Il11ra1 protects against liver steatosis, fibrosis and inflammation while reducing serum glucose, cholesterol and triglyceride levels and limiting obesity. In mice deleted for Il11ra1, restoration of IL11 cis-signaling in hepatocytes reconstitutes steatosis and inflammation but not fibrosis. We found no evidence for the existence of IL6 or IL11 trans-signaling in hepatocytes or NASH. These data show that IL11 modulates hepatocyte metabolism and suggests a mechanism for NAFLD to NASH transition.
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