当前位置： SCI文献检索 > JOURNAL OF HEPATOLOGY期刊下所有文献 > Actin filament formation, reorganization and migration are impaired in hepatic stellate cells under influence of trichostatin A, a histone deacetylase inhibitor.

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

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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Rombouts K,Knittel T,Machesky L,Braet F,Wielant A,Hellemans K,De Bleser P,Gelman I,Ramadori G,Geerts A

doi

10.1016/s0168-8278(02)00275-1

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

788-96

issue

6

eissn

0168-8278

issn

1600-0641

pii

S0168827802002751

journal_volume

37

pub_type

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