Document Detail

Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo.
MedLine Citation:
PMID:  16496318     Owner:  NLM     Status:  MEDLINE    
Hepatic stellate cell activation is a main feature of liver fibrogenesis. We have previously shown that phagocytosis of apoptotic bodies by stellate cells induces procollagen alpha1 (I) and transforming growth factor beta (TGF-beta) expression in vitro. Here we have further investigated the downstream effects of phagocytosis by studying NADPH oxidase activation and its link to procollagen alpha1 (I) and TGF-beta1 expression in an immortalized human stellate cell line and in several models of liver fibrosis. Phagocytosis of apoptotic bodies in LX-1 cells significantly increased superoxide production both in the extracellular and intracellular milieus. By confocal microscopy of LX-1 cells, increased intracellular reactive oxygen species (ROS) were detected in the cells with intracellular apoptotic bodies, and immunohistochemistry documented translocation of the NADPH oxidase p47phox subunit to the membrane. NADPH oxidase activation resulted in upregulation of procollagen alpha1 (I); in contrast, TGF-beta1 expression was independent of NADPH oxidase activation. This was also confirmed by using siRNA to inhibit TGF-beta1 production. In addition, with EM studies we showed that phagocytosis of apoptotic bodies by stellate cells occurs in vivo. In conclusion, these data provide a mechanistic link between phagocytosis of apoptotic bodies, production of oxidative radicals, and the activation of hepatic stellate cells.
Shan-Shan Zhan; Joy X Jiang; Jian Wu; Charles Halsted; Scott L Friedman; Mark A Zern; Natalie J Torok
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  43     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-04-03     Completed Date:  2006-05-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  435-43     Citation Subset:  IM    
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Clinical Nutrition and Vascular Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA.
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MeSH Terms
Apoptosis / physiology*
Cell Line
Collagen Type I / biosynthesis,  genetics
Disease Models, Animal
Hepatitis C / physiopathology
Liver / cytology*,  metabolism*,  physiopathology
Liver Cirrhosis / metabolism*
Microscopy, Confocal
Microscopy, Electron
NADPH Oxidase / metabolism*,  physiology
Oxidative Stress / physiology
Phagocytosis / physiology*
Protein Biosynthesis
RNA Interference
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Transforming Growth Factor beta / biosynthesis,  genetics
Transforming Growth Factor beta1
Grant Support
Reg. No./Substance:
0/Collagen Type I; 0/Reactive Oxygen Species; 0/TGFB1 protein, human; 0/Tgfb1 protein, rat; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; EC Oxidase; EC cytosolic factor 1

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