ArticleNature metabolism2022
BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- The biomedical application of inorganic metal nanoparticles in aging and aging-associated diseases.Journal of advanced research · 2025Pooled it
- Perioperative tislelizumab plus lenvatinib treatment for resectable hepatocellular carcinoma at high risk of recurrence: single-arm phase II trial.Nature communications · 2026Trial
- Association Between Circulating Gremlin 2 and β-Cell Function Among Participants With Prediabetes and Type 2 Diabetes.Journal of diabetes · 2025Trial
- Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial.Nature metabolism · 2026Article
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Serum Gremlin 1 Remains Elevated Following Successful Direct-Acting Antiviral Therapy for Chronic Hepatitis C.Viruses · 2026Article
- Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy.Aging cell · 2026Article
- Human BMP4 mRNA Encapsulated in Lipid Nanoparticle for Bone and Articular Cartilage Repair in Aged Mice.Journal of functional biomaterials · 2026Article
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- Sodium Rutin Ameliorates Non-Alcoholic Fatty Liver Disease and Alleviates Insulin Resistance by Promoting Lipophagy.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Review on the Relationship Between TyG Index and CVD Incidence in Patients With T2DM With NAFLD.International journal of endocrinology · 2026Review
- Integrated Proteogenomic Characterization Identifies Breast Cancer Immune Subgroups and Subtype-Specific Therapeutic Strategies.Research (Washington, D.C.) · 2026Article
- Integrated bioinformatics analysis and experimental validation ofFrontiers in molecular biosciences · 2026Article
- SSRIs-induced liver injury adverse events: a data-based retrospective study and investigation of potential toxicological mechanisms.Frontiers in pharmacology · 2026Article
- Cellular senescence and metabolic aging in type 2 diabetes: mechanistic insights and translational implications.Frontiers in endocrinology · 2026Review
- Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis.Journal of advanced research · 2026Article
- Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting.Journal of hepatology · 2026Review
- Targeting cellular senescence in dystrophinPharmacological research · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets.
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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.