Analysis of HDAC repressor complexes with a function during liverfibrosis.

Project Details


Hepatic fibrosis is a wound-healing response to chronic liver injury, and hepatic stellate cells (HSCs) play a crucial role in this fibrotic response. HSCs from normal liver show a quiescent phenotype storing vitamin A-rich fat droplets. During liver fibrosis, HSCs undergo activation or a transdifferentiation process, which is characterized by loss of intracellular vitamin A stores and change to myofibroblast-like cells with expression of alpha-smooth muscle actin (alpha-SMA). We have shown that histone deacetylase inhibitors can inhibit this process in vitro. The aim of this projectis to unravel the molecular mechanism responsible for this inhibition. We will characterize HDAC complexes involved in the transdifferentiation process by HDAC-complec purifications and characterization from freshly isolated HSCs from adult mice. Their functionwill be studied by using siRNA mediated knock-down in vitro and shRNAmir mediated knock-down in vivo of relevant HDACs and their complexed proteins. To achieve the latter, we will develop lentiviral vectors that specifically express shRNAmirs in stellate cells of the liver by using tissue- and cellspecific promotor/enhancer elements. This will enable us to identify and characterize important transcription complexes necessary for transdifferentiation of hepatic stellate cells in vivo.
Effective start/end date1/01/0931/12/09


  • Fibrosis
  • Hepatic Stellate Cells
  • Histon (de)acetylation
  • Stellate cell activation
  • Liver Cell Transplantation
  • Portal hypertension
  • Sinusoidal Cells
  • Liver Sinusoidal Cells
  • Cell Biology
  • Cytoskeleton
  • Fat-Storing Cells
  • Intermediate Filaments
  • liver stem / progenitor cells
  • Flow Cytometry
  • Metabolic Syndrome
  • Chirrosis

Flemish discipline codes in use since 2023

  • Biological sciences
  • Electrical and electronic engineering
  • Basic sciences


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