Browse by author
Lookup NU author(s): Professor Albert Geerts
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Eukaryotic gene expression has mainly been studied in the context of trans-acting transcription factors and their interaction with regulatory cis-elements. Evidence is accumulating, that the higher order structure of chromatin also plays an essential role in eukaryotic gene expression. Hepatic stellate cells are the major cellular source of extracellular matrix synthesis in chronic liver diseases leading to fibrosis. We explored the antifibrogenic effect of the histone deacetylase inhibitor trichostatin A (TSA) on hepatic stellate cells in vitro. Primary hepatic stellate cells as well as activated, subcultured stellate cells were exposed to 10-7 M - 10-9 M TSA. Collagens type I and III, and smooth muscle α-actin (α-SMA), a marker for transdifferentiation, were investigated at the protein and mRNA level by performing Northern hybridisation and quantitative immunoprecipitation. The antiproliferative effect was examined by 3H-thymidine incorporation and cell counting. Hyperacetylation of histone H4 was demonstrated by acid urea Triton-X-100 (AUT) polyacrylamide gel electrophoresis. TSA at 10-7 M retarded the morphological changes characteristic for activation of primary stellate cells. Synthesis of collagens type I and III, and α-SMA was strongly inhibited at both protein and mRNA level. The proliferation rate of primary hepatic stellate cells was strongly suppressed by 10-7 M TSA. Hyperacetylation of histone H4 showed to be maximal at 10-7 M TSA. Primary hepatic stellate cells were more affected by TSA than subcultured stellate cells.
Author(s): Rombouts K, Niki T, Wielant A, Hellemans K, Geerts A
Publication type: Article
Publication status: Published
Journal: Acta Gastro-Enterologica Belgica
Year: 2001
Volume: 64
Issue: 3
Pages: 239-246
Print publication date: 01/01/2001
ISSN (print): 0001-5644
ISSN (electronic):
Publisher: Universa Press
PubMed id: 11680040
