ArticleHepatology (Baltimore, Md.)2020
Hepatocyte Stress Increases Expression of Yes-Associated Protein and Transcriptional Coactivator With PDZ-Binding Motif in Hepatocytes to Promote Parenchymal Inflammation and Fibrosis.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 152 citations in OpenAlex.
- Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large-Scale Prospective Cohort Study.International journal of cancer · 2026Article
- Review
- Mechanical stiffness orchestrates distinct regulation of MRTFs and YAP/TAZ transcriptional cofactors in hepatocytes.The FEBS journal · 2026Article
- Inflammatory monocytes constrain YAP-induced cell proliferation.Science advances · 2026Article
- New combination therapy of praziquantel andFood and waterborne parasitology · 2026Article
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- A novel bispecific siRNA concept: Efficient dual knockdown ofMolecular therapy. Nucleic acids · 2025Article
- Hepatic stellate cells in liver fibrosis: From biology to pathology.Open veterinary journal · 2025Review
- Alcohol-related hepatitis induces a specific fibrosis profile through YAP activation in myofibroblasts.JHEP reports : innovation in hepatology · 2025Article
- YAP contributes to liver injury through mediating capillarization of liver sinusoidal endothelial cells via GATA6/eNOS signaling.Cellular & molecular biology letters · 2025Article
- Exosomes derived from 3D-cultured hUCMSCs exhibit superior hepatoprotection against ALF.iScience · 2025Article
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Dopamine receptor D1-mediated suppression of liver fibrosisWorld journal of gastroenterology · 2025Article
- MCM7 promotes liver fibrosis by transcriptionally regulating IL11 via the SHCBP1-RACGAP1-STAT3 axis.Cell death & disease · 2025Article
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- Triggering Mechanisms of Hepatocyte Repopulation during Liver Regeneration.Biomolecules & therapeutics · 2025Review
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Baricitinib Mitigates Methotrexate-Induced Liver Fibrosis Model via YAP Pathway.Medicina (Kaunas, Lithuania) · 2025Article
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsActivated hepatocytes are hypothesized to be a major source of signals that drive cirrhosis, but the biochemical pathways that convert hepatocytes into such a state are unclear. We examined the role of the Hippo pathway transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in hepatocytes to facilitate cell-cell interactions that stimulate liver inflammation and fibrosis. APPROACH AND
resultsUsing a variety of genetic, metabolic, and liver injury models in mice, we manipulated Hippo signaling in hepatocytes and examined its effects in nonparenchymal cells to promote liver inflammation and fibrosis. YAP-expressing hepatocytes rapidly and potently activate the expression of proteins that promote fibrosis (collagen type I alpha 1 chain, tissue inhibitor of metalloproteinase 1, platelet-derived growth factor c, transforming growth factor β2) and inflammation (tumor necrosis factor, interleukin 1β). They stimulate expansion of myofibroblasts and immune cells, followed by aggressive liver fibrosis. In contrast, hepatocyte-specific YAP and YAP/TAZ knockouts exhibit limited myofibroblast expansion, less inflammation, and decreased fibrosis after CCl
conclusionsLiver injury in mice and humans increases levels of YAP/TAZ/CYR61 in hepatocytes, thus attracting macrophages to the liver to promote inflammation and fibrosis.
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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.