ArticleHepatology (Baltimore, Md.)2016
Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 183 citations in OpenAlex.
- Hepatic fibrosis extracellular matrix stiffness induces abnormal maturation of dendritic cell via AMPK inhibition-mediated cholesterol accumulation.Materials today. Bio · 2026Article
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- Pilot Study on the Use of Rheology and Low Field Nmr to Characterize the Liver of Obese Patients Undergoing Metabolic and Bariatric Surgery.International journal of molecular sciences · 2026Article
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- Liver-on-a-Chip (LoC) Models: Case Studies of Academic Platforms and Commercial Products.Molecular pharmaceutics · 2026Review
- Mechanical mechanics-reclaiming a new battlefield for chronic liver disease.Journal of advanced research · 2026Review
- Hepatocyte-hepatic stellate cell interactions in liver fibrosis: Mechanisms and therapeutic implications.Hepatology communications · 2026Review
- Mechanical Signaling: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Hepatic hypertension on-a-chip identifies GPR116 as a hydrostatic pressure mechanosensor to regulate vascular injury in cirrhosis.Science advances · 2025Article
- Biochemical and Biophysical Properties of Extracellular Matrix Nanofibers Modulate iPSC-Derived Human Hepatocyte Maturation.Journal of biomedical materials research. Part A · 2025Article
- Liver Fibrosis: Interactions Between Cells and Microenvironments.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Review
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
- Effects of molecular interaction and liver sinusoidal mechanical properties on leukocyte adhesions.Biophysical journal · 2025Article
- Loss of FAM172A gene prompts cell proliferation in liver regeneration.Molecular and cellular biochemistry · 2025Article
- Sacrificial Templating for Accelerating Clinical Translation of Engineered Organs.ACS biomaterials science & engineering · 2025Review
- The influence of biophysical niche on tumor-associated macrophages in liver cancer.Hepatology communications · 2024Review
- Liver mechanosignaling as a natural anti-hepatitis B virus mechanism.Nature communications · 2024Article
- Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats.Scientific reports · 2024Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledMatrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix.
conclusionFibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275).
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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.