Molecular Basis of Fibrogenesis and Angiogenesis During Chronic Liver Disease: Impact of TGF-β and VEGF on Pathogenic Pathways

  • Shinya Mizuno
  • Eriko Osaki


Liver cirrhosis (LC) is pathologically characterized by the loss of functional hepatocytes. The defective area of hepatocytes is replaced with myofibroblast-produced extracellular matrix (ECM) proteins, such as collagens. Transforming growth factor-β (TGF-β) plays multiple roles in LC progression during chronic liver disease. Indeed, TGF-β induces apoptosis and epithelial mesenchymal transition in hepatocytes. Furthermore, TGF-β induces myofibroblastic phenotypes in hepatic stellate cells and sinusoidal endothelial cells for the production of ECMs. TGF-β also contributes to local hypoxia, at least in part, through the induction of endothelin-1, a potent vasoconstrictor. Under such a hypoxic condition, vascular endothelial growth factor (VEGF) is upregulated, followed by neovessel formation, edema and perivascular inflammation (i.e., pathogenic angiogenesis). VEGF and oxidant stress activate latent form TGF-β, resulting in the enhancement of LC, suggesting a crosstalk between pathogenic angiogenesis and fibrosis. In this chapter, we would like to focus on the potential linkage of VEGF-based angiogenesis with TGF-β-enhanced fibrogenesis for understanding of LC-associated pathogenic processes. Not only TGF-β antagonism but also anti-angiogenic therapy may be practical for retarding the progression of LC, a common hallmark of chronic liver disease.


Angiogenesis Cirrhosis Hypoxia Fibrogenesis Myofibroblasts TGF-β 


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Shinya Mizuno
    • 1
    • 2
  • Eriko Osaki
    • 2
  1. 1.Department of Zoology, Faculty of ScienceOkayama University of ScienceOkayamaJapan
  2. 2.Department of Microbiology and ImmunologyOsaka University Graduate School of MedicineSuitaJapan

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