Actin filament formation, reorganization and migration are impaired in hepatic stellate cells under influence of trichostatin A, a histone deacetylase inhibitor

Rombouts, K., Knittel, T., Machesky, L. , Braet, F., Wielant, A., Hellemans, K., De Bleser, P., Gelman, I., Ramadori, G. and Geerts, A. (2002) Actin filament formation, reorganization and migration are impaired in hepatic stellate cells under influence of trichostatin A, a histone deacetylase inhibitor. Journal of Hepatology, 37(6), pp. 788-796. (doi: 10.1016/S0168-8278(02)00275-1) (PMID:12445420)

Full text not currently available from Enlighten.

Abstract

Background/Aims: Previously, trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to exhibit strong antifibrotic characteristics in hepatic stellate cells (HSC), which are known to play a central role in chronic liver diseases. TSA retained a more quiescent phenotype in spite of culture conditions that favor transdifferentiation into activated HSC. Methods: To identify TSA-sensitive genes, differential mRNA display, Northern and Western blot analysis were used and genes were functionally validated by using contraction and motility assays. Results: TSA prevented new actin filament formation by down-regulation of two nucleating proteins, actin related protein 2 (Arp2) and Arp3, and by up-regulation of adducin like protein 70 (ADDL70) and gelsolin, two capping proteins. RhoA, a key mediator in the development of the actin cytoskeleton, decreased following TSA exposure. Expression of proteins of Class III intermediate filaments was affected by TSA. Furthermore, F-actin and G-actin were expressed heterogeneously under influence of TSA. Functionally, TSA treatment abrogated migration of quiescent HSC, while migration was reduced in transitional HSC. The endothelin-1-induced contractility properties of HSC was not affected by TSA. Conclusions: These data indicate that TSA affects the development of the actin cytoskeleton in quiescent HSC and thereby abrogates the process of HSC transdifferentiation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura
Authors: Rombouts, K., Knittel, T., Machesky, L., Braet, F., Wielant, A., Hellemans, K., De Bleser, P., Gelman, I., Ramadori, G., and Geerts, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Hepatology
Publisher:Elsevier
ISSN:0168-8278
ISSN (Online):1600-0641
Published Online:04 September 2002

University Staff: Request a correction | Enlighten Editors: Update this record