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

Authors: Rombouts, Krista  Knittel, Thomas  Machesky, Laura  Braet, Filip  Wielant, Annemie  Hellemans, Karine  De Bleser, Pieter  Gelman, Irwin  Ramadori, Giuliano  Geerts, Albert 
Citation: Rombouts K, etal., J Hepatol. 2002 Dec;37(6):788-96.
Pubmed: (View Article at PubMed) PMID:12445420


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.

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CRRD Object Information
CRRD ID: 632492
Created: 2003-08-29
Species: All species
Last Modified: 2003-08-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.