ArticleJournal of hepatology2022
Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo.
Article in Journal of hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 80 citations in OpenAlex.
- H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads.International journal of oral science · 2026Article
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.Hepatology (Baltimore, Md.) · 2026Article
- Dynamic hydrogels orchestrate the differentiation fate of mesenchymal stem cells through epigenetic regulation of SETD7 to accelerate bone defect repair.Bioactive materials · 2026Article
- Liver sinusoidal endothelial cell fenestrations in metabolic liver disease: from molecular mechanisms to therapeutic perspectives.Cell communication and signaling : CCS · 2026Review
- Mechanisms of actin-binding proteins in glycolysis-cytoskeleton coupling.Journal of translational medicine · 2026Review
- Epigenetic drug control of Clec4g/LSECtin expression reduces fibrosis burden in cirrhosis.Hepatology communications · 2026Article
- Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Sinusoidal endothelial cells control liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- P38γ drives aerobic glycolysis in liver sinusoidal endothelial cells and regulates alcoholic liver disease via the PFKFB3 signaling pathway.Molecular biology reports · 2026Article
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Review
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Development of cell-active BRD4-D1 selective inhibitors to decode the role of BET proteins in LPS-mediated liver inflammation.European journal of medicinal chemistry · 2026Article
- MSCs-derived CRABP2 regulates Treg/CXCL1 to ameliorate alcohol-induced liver injury.Cell communication and signaling : CCS · 2026Article
- Epigenetic reprogramming of hepatic antigen presenting cells in chronic liver disease.Frontiers in immunology · 2026Review
- Article
- Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsLiver sinusoidal endothelial cells (LSECs) are ideally situated to sense stiffness and generate angiocrine programs that potentially regulate liver fibrosis and portal hypertension. We explored how specific focal adhesion (FA) proteins parlay LSEC mechanotransduction into stiffness-induced angiocrine signaling in vitro and in vivo.
methodsPrimary human and murine LSECs were placed on gels with incremental stiffness (0.2 kPa vs. 32 kPa). Cell response was studied by FA isolation, actin polymerization assay, RNA-sequencing and electron microscopy. Glycolysis was assessed using radioactive tracers. Epigenetic regulation of stiffness-induced genes was analyzed by chromatin-immunoprecipitation (ChIP) analysis of histone activation marks, ChIP sequencing and circularized chromosome conformation capture (4C). Mice with LSEC-selective deletion of glycolytic enzymes (Hk2
resultsGlycolytic enzymes, particularly phosphofructokinase 1 isoform P (PFKP), are enriched in isolated FAs from LSECs on gels with incremental stiffness. Stiffness resulted in PFKP recruitment to FAs, which paralleled an increase in glycolysis. Glycolysis was associated with expansion of actin dynamics and was attenuated by inhibition of integrin β1. Inhibition of glycolysis attenuated a stiffness-induced CXCL1-dominant angiocrine program. Mechanistically, glycolysis promoted CXCL1 expression through nuclear pore changes and increases in NF-kB translocation. Biochemically, this CXCL1 expression was mediated through spatial re-organization of nuclear chromatin resulting in formation of super-enhancers, histone acetylation and NF-kB interaction with the CXCL1 promoter. Hk2
conclusionGlycolytic enzymes are involved in stiffness-induced angiocrine signaling in LSECs and represent druggable targets in early liver disease. LAY SUMMARY: Treatment options for liver fibrosis and portal hypertension still represent an unmet need. Herein, we uncovered a novel role for glycolytic enzymes in promoting stiffness-induced angiocrine signaling, which resulted in inflammation, fibrosis and portal hypertension. This work has revealed new targets that could be used in the prevention and treatment of liver fibrosis and portal hypertension.
Indexed as
Identifiers
What OpenQuestion holds
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.