- •Increased stiffness leads to recruitment of glycolytic enzymes to focal adhesions in LSECs, paralleling an increase in glycolysis.
- •Inhibition of glycolysis blocks a stiffness-induced CXCL1-dominant angiocrine program.
- •Glycolysis promotes CXCL1 expression through nuclear pore changes and increases in NF-kB translocation.
- •LSEC-selective deletion of glycolytic enzymes results in attenuation of portal hypertension in vivo.
- •Treatment with the glycolysis inhibitor 3PO attenuates early liver fibrosis in vivo.
Background & Aims
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights.J Gastroenterol. 2016; 51: 511-519
- Lipopolysaccharide signaling in endothelial cells.Lab Invest. 2006; 86: 9-22
- Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines.Hepatology. 2008; 48: 1262-1272
- Angiocrine signaling in the hepatic sinusoids in health and disease.Am J Physiol Gastrointest Liver Physiol. 2016; 311: G246-G251
- Mechanical stretch increases expression of CXCL1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension.Gastroenterology. 2019; 157: 193-209.e9
- Tissue mechanics and fibrosis.Biochim Biophys Acta. 2013; 1832: 884-890
- Mechanotransduction and fibrosis.J Biomech. 2014; 47: 1997-2005
- Mechanotransduction and extracellular matrix homeostasis.Nat Rev Mol Cell Biol. 2014; 15: 802-812
- Integrins in mechanotransduction.Curr Opin Cell Biol. 2013; 25: 613-618
- Stretching single talin rod molecules activates vinculin binding.Science. 2009; 323: 638-641
- Integrin α4β1 controls G9a activity that regulates epigenetic changes and nuclear properties required for lymphocyte migration.Nucleic Acids Res. 2016; 44: 3031-3044
- Mechanosensitive components of integrin adhesions: role of vinculin.Exp Cell Res. 2016; 343: 21-27
- Role of PFKFB3-driven glycolysis in vessel sprouting.Cell. 2013; 154: 651-663
- FGF-dependent metabolic control of vascular development.Nature. 2017; 545: 224-228
- Force triggers YAP nuclear entry by regulating transport across nuclear pores.Cell. 2017; 171: 1397-1410.e14
- The NF-kappa B and I kappa B proteins: new discoveries and insights.Annu Rev Immunol. 1996; 14: 649-683
- NF-kappaB: a key role in inflammatory diseases.J Clin Invest. 2001; 107: 7-11
- Activation of NF-kappaB by fluid shear stress, but not TNF-alpha, requires focal adhesion kinase in osteoblasts.Bone. 2010; 47: 74-82
- YAP1 exerts its transcriptional control via TEAD-mediated activation of enhancers.Plos Genet. 2015; 11e1005465
- P300 acetyltransferase mediates stiffness-induced activation of hepatic stellate cells into tumor-promoting myofibroblasts.Gastroenterology. 2018; 154: 2209-2221.e14
- Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions.Nat Genet. 2006; 38: 1341-1347
- What are super-enhancers?.Nat Genet. 2015; 47: 8-12
- Master transcription factors and mediator establish super-enhancers at key cell identity genes.Cell. 2013; 153: 307-319
- Super-enhancers in the control of cell identity and disease.Cell. 2013; 155: 934-947
- Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces.Hepatology. 2015; 61: 648-659
- Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis.Nat Commun. 2021; 12: 4560
- Properties of the interaction between phosphofructokinase and actin.Arch Biochem Biophys. 1989; 269: 284-294
- Targeting a moonlighting function of aldolase induces apoptosis in cancer cells.Cell Death Dis. 2019; 10: 712
- YAP nuclear localization in the absence of cell-cell contact is mediated by a filamentous actin-dependent, myosin II- and phospho-YAP-independent pathway during extracellular matrix mechanosensing.J Biol Chem. 2016; 291: 6096-6110
- A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors.Cell. 2013; 154: 1047-1059
- Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity.Nat Cell Biol. 2016; 18: 540-548
- Nuclear deformation mediates liver cell mechanosensing in cirrhosis.JHEP Rep. 2020; 2: 100145
- Glycolytic reprogramming in myofibroblast differentiation and lung fibrosis.Am J Respir Crit Care Med. 2015; 192: 1462-1474
- Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis.Nat Mater. 2017; 16: 1252-1261
- Role and therapeutic potential of vascular stem/progenitor cells in pathological neovascularisation during chronic portal hypertension.Gut. 2017; 66: 1306-1320
- Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis.Gut. 2017; 66: 145-155
- Lipid-induced endothelial vascular cell adhesion molecule 1 promotes nonalcoholic steatohepatitis pathogenesis.J Clin Invest. 2021; 131
- Liver sinusoidal endothelial cell lectin, LSECtin, negatively regulates hepatic T-cell immune response.Gastroenterology. 2009; 137: 1498-1508.e1-5
- Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes.Hepatology. 2006; 43: 257-265
Author names in bold designate shared co-first authorship