ArticleScience translational medicine2023
An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 150 citations in OpenAlex.
- Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology.Liver international : official journal of the International Association for the Study of the Liver · 2024Trial
- Altered cholangiocyte subsets with neural pathway enrichment in metabolic dysfunction-associated steatotic liver disease.Internal and emergency medicine · 2026Article
- A human single-cell atlas identifies OLR1Nature genetics · 2026Article
- ITGBL1-MYH9 interaction in hepatic stellate cells acts as a mechanoregulator controlling liver fibrosis in mice.The Journal of clinical investigation · 2026Article
- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Hepatic stellate cell subpopulations in human MASLD-related hepatocellular carcinoma upregulate YAP via geranylgeranyl pyrophosphate.Hepatology communications · 2026Article
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Procollagen 1 assembles into phase-separated condensates in the endoplasmic reticulum.The Journal of cell biology · 2026Article
- A minimal model of PTSD susceptibility and timescales.iScience · 2026Article
- Pulmonary arterial hypertension induces a metabolic and inflammatory hepatopathy.The Journal of clinical investigation · 2026Article
- NAT10 promotes the activation of hepatic stellate cells by modulating the TGF-β1-ac4C-COL1A1 axis.Hepatology international · 2026Article
- Unveiling novel macrophage-specific biomarkers in MASH through single-cell sequencing for diagnostic modeling.Journal of lipid research · 2026Article
- Metabolic dysfunction-associated steatotic liver disease: pathogenesis and novel treatment options.Molecular biomedicine · 2026Review
- Review
- Fibroblast growth factor 10 attenuates advanced liver fibrosis through hepatocyte fibroblast growth factor receptor 2 signalling.Clinical and translational medicine · 2026Article
- Article
- Single-cell fixed RNA profiling uncovers SEMA4D and LMCD1 as therapeutic targets in a liver fibrosis model.JHEP reports : innovation in hepatology · 2026Article
- Single-cell profiling reveals hepatic monocyte-derived macrophages heterogeneity during steatotic liver disease.Hepatology communications · 2026Article
- Magnesium-tannic acid nanomedicines reprogram pro-fibrotic macrophages for hepatic fibrosis treatment via restoring endoplasmic reticulum homeostasis.Journal of nanobiotechnology · 2026Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
Advanced hepatic fibrosis, driven by the activation of hepatic stellate cells (HSCs), affects millions worldwide and is the strongest predictor of mortality in nonalcoholic steatohepatitis (NASH); however, there are no approved antifibrotic therapies. To identify antifibrotic drug targets, we integrated progressive transcriptomic and morphological responses that accompany HSC activation in advanced disease using single-nucleus RNA sequencing and tissue clearing in a robust murine NASH model. In advanced fibrosis, we found that an autocrine HSC signaling circuit emerged that was composed of 68 receptor-ligand interactions conserved between murine and human NASH. These predicted interactions were supported by the parallel appearance of markedly increased direct stellate cell-cell contacts in murine NASH. As proof of principle, pharmacological inhibition of one such autocrine interaction, neurotrophic receptor tyrosine kinase 3-neurotrophin 3, inhibited human HSC activation in culture and reversed advanced murine NASH fibrosis. In summary, we uncovered a repertoire of antifibrotic drug targets underlying advanced fibrosis in vivo. The findings suggest a therapeutic paradigm in which stage-specific therapies could yield enhanced antifibrotic efficacy in patients with advanced hepatic fibrosis.
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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.