In Vivo Evaluation of the Antifibrogenic Properties of Trichostatin A and Analogues.

  • Geerts, Albert, (Administrative Promotor)

Project Details

Description

Two years ago, we discovered that trichostatin A (TSA) is a potent antifibrogenic agent in cultures of stellate cells and skin fibroblasts. TSA retards the morphological changes during activation of stellate cells, suppresses synthesis of collagens I and III, inhibits expression of alpha-smooth muscle actin and cellular proliferation, and blunts TGF-beta induced ECM production. Because the external supply of TSA was very limited, Prof. A. Geerts and Prof. Dr. D. Tourwé started a program to synthesize larger quantities of TSA as well as TSA analogues with grant support of the research council of VUB and IWT. In parallel with these synthetic efforts, Lic. J. Kestemont, Dr. W. WU and Prof. A. Geerts adapted the well-known CCl4 model of fibrosis to Balb/c mice, installed the necessary computer hardware and developed the software to quantify fibrosis by morphometry in 10nanometer cryostat sections stained with picrosirius. Soon newly synthesized compounds will be tested in vivo for their antifibrogenic properties. This project is complementary to the existing OZR project 1 96 322 1120. It is aimed at finding 50% funding to replace a defective eight year old cryostat microtome. A cryostat microtome is indispensable for the above project. This microtome will also be used in other parts of the fibrosis project (FGF-beta, cytoskeleton, retinoids, somatostatin receptors) as well as by the research group of Prof. Dr. C. Van den Branden.
AcronymOZR312
StatusFinished
Effective start/end date1/01/9931/12/99

Flemish discipline codes

  • Basic sciences
  • Pharmaceutical sciences

Keywords

  • Cirrhosis
  • Hepatic Fibrosis
  • Morphometry
  • Hepatic Stellate Cells
  • Collagen