ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1-YAP Mechanotransduction.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed.
- Peroxisome proliferator-activated receptor gamma (PPARγ) as a mechano-metabolic transducer: coordinating lipid homeostasis through mechanical cues.Molecular biomedicine · 2026Review
- Review
- Stiffness-Activated Stellate Cells Drive Pancreatic Cancer Liver Colonization via GMFG-TNS4 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Liver sinusoidal endothelial cell fenestrations in metabolic liver disease: from molecular mechanisms to therapeutic perspectives.Cell communication and signaling : CCS · 2026Review
- Hepatocyte PIEZO1 Negatively Regulates Lipogenesis and Ameliorates MASLD by Sensing Membrane Tension and Activating AMPK.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation.Biology · 2026Review
- Calcium imbalance drives organelle network collapse and immune remodeling: novel pathogenic mechanisms in MASLD progression.Frontiers in immunology · 2026Review
- Liver cirrhosis and hepatocellular carcinoma: chronological decoupling of biochemical clearance and mechanical regeneration signals a systems biology hypothesis on programed deconstruction failure.Frontiers in oncology · 2026Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is shaped by metabolic injury and tissue mechanics. This study investigated whether liver stiffening occurs early in MASLD and how extracellular matrix (ECM) mechanics interact with lipid droplet (LD) overload to promote inflammation, fibrogenesis, and lipid dysmetabolism. Clinical data, mouse models, and in vitro experiments are integrated. Liver stiffness shifted modestly with steatosis but increased substantially in the presence of inflammation. In a diet-induced mouse model, liver stiffness increased before overt fibrosis. In cultured hepatocytes, stiff matrices combined with free fatty acid (FFA) induced steatosis synergistically amplified pro-inflammatory and pro-fibrotic signals, accompanied by cytoskeletal remodeling and nuclear deformation. YAP acted as a central mechanosensitive amplifier: stiffness drove YAP nuclear localization, and YAP knockdown blunted cytokine induction and fibrogenic gene expression under stiff + FFA conditions. Stiffness and LD overload jointly promoted lipogenesis and impaired lipophagy via YAP. Piezo1 is upregulated by stiff + FFA; its inhibition reduced Ca
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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 Socratic graph.