Document Detail

Role of Rho small GTP binding protein in the regulation of actin cytoskeleton in hepatic stellate cells.
MedLine Citation:
PMID:  10424288     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: In the fibrotic response to liver injury, hepatic stellate cells are activated, leading to the myofibroblastic cell shape, with actin cytoskeletal reorganization and increased extracellular matrix production. The reorganization of actin cytoskeleton suggests that the small GTP binding protein Rho might modulate the process of this myofibroblastic change. The aim of this study was to investigate the role of Rho in the phenotypic changes of hepatic stellate cells. METHODS: The phenotypic changes were investigated by the overexpression of Rho regulator, Rho GDI or dominant negative mutant of Rho in mouse hepatic stellate cell line, GRX cells. In activated rat hepatic stellate cells, the effects of microinjection of Botulinus toxin C3, which is the specific inhibitor for Rho, were analyzed. Furthermore, the effect of C3 on the type I collagen accumulation in hepatic stellate cells was investigated. RESULTS: Overexpression of Rho GDI or the dominant negative mutant of Rho caused the shrinkage cell shape and suppressed stress fiber formation. Microinjection of toxin C3 caused a markedly distorted cell shape and the disappearance of stress fibers in rat stellate cells. In addition, C3 strongly suppressed collagen accumulation in activated stellate cells. CONCLUSIONS: These results suggest that Rho regulates the actin cytoskeletal reorganization, and may be implicated in the collagen accumulation in activated stellate cells. These findings provide evidence for the role of Rho in the myofibroblastic phenotype in hepatic stellate cells.
M Kato; H Iwamoto; N Higashi; R Sugimoto; K Uchimura; S Tada; H Sakai; M Nakamuta; H Nawata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  31     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-09-07     Completed Date:  1999-09-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  91-9     Citation Subset:  IM    
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Actins / metabolism*
Cell Line
Cell Size
Cells, Cultured
Collagen / metabolism
Cytoskeleton / drug effects,  physiology*,  ultrastructure
GTP-Binding Proteins / genetics,  metabolism*
Guanine Nucleotide Dissociation Inhibitors*
Guanine Nucleotides / metabolism
Liver / cytology,  physiology*
Rats, Wistar
Recombinant Proteins / metabolism
rhoA GTP-Binding Protein
Reg. No./Substance:
0/Actins; 0/Guanine Nucleotide Dissociation Inhibitors; 0/Guanine Nucleotides; 0/Recombinant Proteins; 133312-85-3/rho guanine nucleotide dissociation inhibitors; 9007-34-5/Collagen; EC 3.6.1.-/GTP-Binding Proteins; EC GTP-Binding Protein

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