Portal hypertension is a dreaded complication of cirrhosis and is characterized by an increased pressure in the portal vein. It is generally accepted that hepatic stellate cells (HSC) play a key role in the pathogenesis of portal hypertension: by contracting they augment intra-hepatic vascular resistance.
Whereas contraction/relaxation of smooth muscle cells is primarily regulated by changes in [Ca²+]i, contractility of non-muscle cells is controlled by RhoA signal transduction. It is clear that both mechanisms are involved in HSC contractility. In order to transmit contractile forces, cells need a firm cytoskeleton and anchoring in the extracellular matrix. In skeletal muscle , the dystrophin-associated protein complex (DAPC) is the physical and functional link between extracellular matrix and actin-myosin filaments on the one hand, and intermediate filaments on the other hand. Moreover, in aorta smooth muscle cells the degree of contractility is proportional to the content of dystrophin. In preliminary experiments we have shown that several components of the DAPC are up-regulated during activation of HSC. We postulate that increased contractility of HSC during activation is, at least partially, caused by up-regulation of the DAPC. The goal of this research project is to increase our knowledge of the mechanisms involved in HSC contraction, and more specifically the role of DAPC in stellate cell contraction.
Effective start/end date1/01/1031/12/10

    Flemish discipline codes

  • Basic sciences
  • Biological sciences
  • Materials engineering

    Research areas

  • Tonic Pain, Dendritic Cells, Evoked Potentials, Bispecific Antibodies, Immunotherapy, Immunology, Oncology

ID: 3323924