ArticleCell metabolism2022
Neuregulin 4 suppresses NASH-HCC development by restraining tumor-prone liver microenvironment.
Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Pooled it
- Role of adipocytes and their derived extracellular vesicles in the progression, diagnosis and treatment of liver diseases (Review).International journal of molecular medicine · 2026Review
- Cancer-associated adipocytes: metabolic reprogramming, crosstalk and therapeutic implications in tumor progression.Signal transduction and targeted therapy · 2026Review
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- NRG4 suppresses breast cancer metastasis via ERBB4-YAP1-mediated down-regulation of MMPs.Genes & diseases · 2026Article
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- Regulation of immune tolerance in hepatocellular carcinoma by liver diseases: a review.Infectious agents and cancer · 2026Review
- SLC13A2-transported citrate remodels transcriptional regulation through protein acetylation to suppress tumor growth.Science advances · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Targeting STE20-type kinase MST3 improves metabolic dysfunction-associated steatohepatitis without affecting hepatocellular carcinoma development in mice.BMC medicine · 2026Article
- Molecular mechanisms of tumor-associated macrophages in hepatocellular carcinoma development and therapy.World journal of gastroenterology · 2026Review
- Single-Cell Analysis of Hepatic Non-Parenchymal Cells Reveals Endothelial Dysfunction and Altered Endothelial and B Cell Communication in Acute-on-Chronic Liver Failure.Journal of immunology research · 2026Article
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- The impact of chronic comorbidities on cancer immunoediting: challenges and opportunities for immunotherapies.Frontiers in immunology · 2026Review
- Adipokine in Metabolic Liver Disease: Adipo-Brain-Liver Cross talk.International journal of endocrinology · 2026Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Neuregulin 4 inhibits synovial macrophage pro-inflammatory polarization via ErbB4/Stat5b/NF-κB signaling to alleviate osteoarthritis progression.Journal of orthopaedic surgery and research · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Myeloid TGF-β signaling shapes liver macrophage heterogeneity and metabolic liver disease pathogenesis.JHEP reports : innovation in hepatology · 2025Article
9 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
17 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian liver comprises heterogeneous cell types within its tissue microenvironment that undergo pathophysiological reprogramming in disease states, such as non-alcoholic steatohepatitis (NASH). Patients with NASH are at an increased risk for the development of hepatocellular carcinoma (HCC). However, the molecular and cellular nature of liver microenvironment remodeling that links NASH to liver carcinogenesis remains obscure. Here, we show that diet-induced NASH is characterized by the induction of tumor-associated macrophage (TAM)-like macrophages and exhaustion of cytotoxic CD8+ T cells in the liver. The adipocyte-derived endocrine factor Neuregulin 4 (NRG4) serves as a hormonal checkpoint that restrains this pathological reprogramming during NASH. NRG4 deficiency exacerbated the induction of tumor-prone liver immune microenvironment and NASH-related HCC, whereas transgenic NRG4 overexpression elicited protective effects in mice. In a therapeutic setting, recombinant NRG4-Fc fusion protein exhibited remarkable potency in suppressing HCC and prolonged survival in the treated mice. These findings pave the way for therapeutic intervention of liver cancer by targeting the NRG4 hormonal checkpoint.
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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.