Document Detail


c-Myb modulates transcription of the alpha-smooth muscle actin gene in activated hepatic stellate cells.
MedLine Citation:
PMID:  10666057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of alpha-smooth muscle actin (alpha-SMA) defines the phenotype of activated (myofibroblastic) hepatic stellate cells. These cells, but not quiescent stellate cells, have a high level of alpha-SMA and c-Myb expression, as well as increased c-Myb-binding activities to the proximal alpha-SMA E box. Therefore, we analyzed the role of c-Myb in alpha-SMA transcription and stellate cell activation. Activated primary rat stellate cells displayed a high expression of the -724 and -271 alpha-SMA/luciferase (LUC) chimeric genes, which contain c-Myb binding sites (-223/-216 bp). Alpha-SMA/LUC minigenes with mutation (-219/-217 bp), truncation (-224 bp), or deletion (-191 bp) of the c-Myb binding site were not efficiently transcribed. Transfection of wild-type c-Myb into quiescent stellate cells, which do not express endogenous c-Myb, induced a approximately 10-fold stimulation of -724 alpha-SMA/LUC expression. Conversely, expression of either a dominant-negative c-Myb basic domain mutant (Cys(43) --> Asp) or a c-Myb antisense RNA blocked transcription from the -724 alpha-SMA/LUC or -271 alpha-SMA/LUC in activated cells. Moreover, transfection of c-myb antisense, but not sense, RNA inhibited both expression of the endogenous alpha-SMA gene and stellate cell activation, whereas transfection of c-myb stimulated alpha-SMA expression in quiescent stellate cells. These findings suggest that c-Myb modulates the activation of stellate cells and that integrity of the redox sensor Cys(43) in c-Myb is required for this effect.
Authors:
M Buck; D J Kim; K Houglum; T Hassanein; M Chojkier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  278     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-02     Completed Date:  2000-03-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  G321-8     Citation Subset:  IM    
Affiliation:
Department of Medicine, Veterans Affairs Medical Center, San Diego, California 92161, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics*
Animals
Cells, Cultured
Fluorescent Antibody Technique
Gene Expression Regulation*
Liver / cytology,  metabolism*
Male
Point Mutation
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myb / genetics,  physiology*
RNA, Antisense
Rats
Rats, Sprague-Dawley
Regulatory Sequences, Nucleic Acid
Transcription, Genetic / drug effects
Transfection
Grant Support
ID/Acronym/Agency:
DK-38652/DK/NIDDK NIH HHS; DK-46971/DK/NIDDK NIH HHS; GM-47165/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Proto-Oncogene Proteins c-myb; 0/RNA, Antisense

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