ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
Hepatic stellate cells require a stiff environment for myofibroblastic differentiation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers, 1 of them a synthesis that pooled it.
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Who cites it
215 citing papers in PubMed, 1 synthesis or guideline pooled it.
- High throughput interrogation of human liver stellate cells reveals microenvironmental regulation of phenotype.Acta biomaterialia · 2022Pooled it
- Mechanical stiffness orchestrates distinct regulation of MRTFs and YAP/TAZ transcriptional cofactors in hepatocytes.The FEBS journal · 2026Article
- Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Matrix stiffness shapes early transcriptional trajectories during hepatic stellate cell activation.Hepatology international · 2026Article
- Therapeutic Mechanisms of Resmetirom and Semaglutide in MASLD/MASH: A Review of Inflammatory and Fibrotic Metabolites.Metabolites · 2026Review
- Loss of CD44 re-educates pancreatic cancer-associated fibroblasts modulating their fibrotic and immunosuppressive functions.Cell death & disease · 2026Article
- 3D Liver Fibrosis Models in Lab: A Novel Modality for Drug Screening.Pharmacology research & perspectives · 2026Review
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency.bioRxiv : the preprint server for biology · 2026Article
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- Questions and comments on "ALKBH5 attenuates mitochondrial fission and ameliorates liver fibrosis by reducing Drp1 methylation," published in Pharmacological Research (2023).Pharmacological research · 2026Article
- Cholesterol-containing lipid crystals can directly stiffen the rat steatotic liver before fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- Engineered mesenchymal stem cell-derived extracellular vesicles as programmable biomaterial platforms for liver fibrosis: design principles, manufacturing and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease.Molecular therapy. Nucleic acids · 2025Review
- Article
- Stiffness-activated hepatic stellate cells boost HCC migration via TGM2/ITGB1-mediated matrix remodeling and mitochondrial transfer.JHEP reports : innovation in hepatology · 2025Article
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Increased matrix stiffness promotes fibrogenesis of hepatic stellate cells through AP-1-induced chromatin priming.Communications biology · 2025Article
155 more citing papers are in PubMed but not listed here.
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9 authors.
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Abstract
The myofibroblastic differentiation of hepatic stellate cells (HSC) is a critical event in liver fibrosis and is part of the final common pathway to cirrhosis in chronic liver disease from all causes. The molecular mechanisms driving HSC differentiation are not fully understood. Because macroscopic tissue stiffening is a feature of fibrotic disease, we hypothesized that mechanical properties of the underlying matrix are a principal determinant of HSC activation. Primary rat HSC were cultured on inert polyacrylamide supports of variable but precisely defined shear modulus (stiffness) coated with different extracellular matrix proteins or poly-L-lysine. HSC differentiation was determined by cell morphology, immunofluorescence staining, and gene expression. HSC became progressively myofibroblastic as substrate stiffness increased on all coating matrices, including Matrigel. The degree rather than speed of HSC activation correlated with substrate stiffness, with cells cultured on supports of intermediate stiffness adopting stable intermediate phenotypes. Quiescent cells on soft supports were able to undergo myofibroblastic differentiation with exposure to stiff supports. Stiffness-dependent differentiation required adhesion to matrix proteins and the generation of mechanical tension. Transforming growth factor-β treatment enhanced differentiation on stiff supports, but was not required. HSC differentiate to myofibroblasts in vitro primarily as a function of the physical rather than the chemical properties of the substrate. HSC require a mechanically stiff substrate, with adhesion to matrix proteins and the generation of mechanical tension, to differentiate. These findings suggest that alterations in liver stiffness are a key factor driving the progression of fibrosis.
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