Document Detail


Preservation of basal AcSDKP attenuates carbon tetrachloride-induced fibrosis in the rat liver.
MedLine Citation:
PMID:  20646773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous tetrapeptide which has antifibrogenic effects at physiological concentrations in various tissues. AcSDKP is produced locally in the liver, however, little is known about its biological effect in this organ. We hypothesize that basal levels of endogenous AcSDKP decrease during the development of liver fibrosis and preservation of basal AcSDKP attenuates liver fibrosis.
METHODS: Endogenous levels of AcSDKP in the liver were measured by enzyme immunoassay after 2, 6, and 10 weeks of carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. Subcutaneous osmotic pump infusion of vehicle or AcSDKP (800 microg/kg/day) was administered to CCl(4)-treated rats for 8 weeks to study the effect of exogenous AcSDKP on liver fibrosis. The effect of AcSDKP on profibrogenic properties of hepatic stellate cells was studied in vitro.
RESULTS: Endogenous AcSDKP was significantly decreased in the liver of CCl(4)-treated rats. Chronic AcSDKP infusion preserved basal levels of AcSDKP and reduced liver injury, inflammation, fibrosis, and profibrogenic transforming growth factor-beta signaling. This was demonstrated by decreased aminotransferase serum levels, CD45 positive cells, collagen accumulation, alpha-smooth muscle actin positivity, transforming growth factor-beta1, phosphorylated Smad2/3 protein, increased bone morphogenetic protein-7, and phosphorylated Smad1/5/8. Further, AcSDKP exerts antifibrogenic effects on hepatic stellate cells (HSCs) by downregulation of HSC activation in vitro.
CONCLUSIONS: Maintaining physiological levels of AcSDKP is critical in negatively regulating the development of fibrosis in chronic liver injury. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
Authors:
Yuan-Wen Chen; Bo-Wei Liu; Yu-Jian Zhang; Ying-Wei Chen; Guo-Fang Dong; Xiao-Dong Ding; Lei-Ming Xu; Betty Pat; Jiang-Gao Fan; Ding-Guo Li
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-31
Journal Detail:
Title:  Journal of hepatology     Volume:  53     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-17     Completed Date:  2010-12-07     Revised Date:  2012-08-24    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  528-36     Citation Subset:  IM    
Copyright Information:
Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Affiliation:
Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Carbon Tetrachloride Poisoning / metabolism*,  pathology,  prevention & control
Collagen / genetics
Gene Expression / drug effects
Hepatic Stellate Cells / drug effects,  metabolism,  pathology
Liver Cirrhosis, Experimental / chemically induced,  metabolism*,  pathology,  prevention & control
Male
Oligopeptides / metabolism*,  pharmacology
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects
Transforming Growth Factor beta / metabolism
Chemical
Reg. No./Substance:
0/Actins; 0/Oligopeptides; 0/Transforming Growth Factor beta; 0/smooth muscle actin, rat; 120081-14-3/goralatide; 9007-34-5/Collagen

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