Document Detail


Hydrogen peroxide is a novel inducer of connective tissue growth factor.
MedLine Citation:
PMID:  11409888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Connective tissue growth factor (CTGF) has recently been described as a fibrogenic factor and is greatly induced by various extracellular stimuli, such as transforming growth factor-beta (TGF-beta), dexamethasone, and serotonin. CTGF induces collagen type I and fibronectin, and the deposition of such molecules leads to fibrotic disease in many tissues. Intracellular reactive oxygen species (ROS) are generated by extracellular stress conditions and are produced as by-products of cellular metabolism. Imbalanced cellular redox status is a potent pathogenic factor that leads to various degenerative diseases, including tissue fibrosis. Since CTGF is believed to play a crucial role in fibrotic disease formation in many tissues, we examined the role of ROS in CTGF gene expression in human lens epithelial cell line B3. The results showed that CTGF was induced by reactive oxygen species such as hydrogen peroxide and hydroxyl radicals. Next, we examined whether CTGF induction by ROS is via newly synthesized TGF-beta. The results showed that ROS directly induced CTGF mRNA not via the increased TGF-beta synthesis or activation. Next, we treated AG490, which is the well-known inhibitor of Janus kinase (JAK), with hydrogen peroxide. AG490 abrogated the CTGF induction by ROS in a dose-dependent manner. The results suggest that JAK-2/-3 seems to be involved in the enhanced CTGF mRNA expression by hydrogen peroxide. In this report, we present that hydrogen peroxide is a novel inducer of CTGF gene expression and that JAK-2/-3 activation seems to play a role in CTGF induction.
Authors:
S K Park; J Kim; Y Seomun; J Choi; D H Kim; I O Han; E H Lee; S K Chung; C K Joo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  284     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-18     Completed Date:  2001-07-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  966-71     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Laboratory of Ophthalmology and Visual Science, The Catholic University of Korea, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Blotting, Western
Cell Line
Connective Tissue Growth Factor
Dexamethasone / pharmacology
Enzyme Inhibitors / pharmacology
Epithelial Cells / cytology,  drug effects,  metabolism*
Gene Expression Regulation / drug effects
Growth Substances / analysis,  genetics*
Humans
Hydrogen Peroxide / pharmacology*
Immediate-Early Proteins / analysis,  genetics*
Intercellular Signaling Peptides and Proteins*
Lens, Crystalline / cytology,  metabolism*
Molecular Sequence Data
Peptide Fragments / chemistry,  immunology
Protein-Tyrosine Kinases / antagonists & inhibitors
Tyrphostins / pharmacology
Chemical
Reg. No./Substance:
0/CTGF protein, human; 0/Enzyme Inhibitors; 0/Growth Substances; 0/Immediate-Early Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Peptide Fragments; 0/Tyrphostins; 0/alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; 139568-91-5/Connective Tissue Growth Factor; 50-02-2/Dexamethasone; 7722-84-1/Hydrogen Peroxide; EC 2.7.10.1/Protein-Tyrosine Kinases

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