Document Detail

Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion.
MedLine Citation:
PMID:  9722209     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Kupffer cells are located in the liver sinusoids adjacent to hepatocytes and elaborate a range of growth regulatory molecules involved in regulating hepatocyte proliferation. In vitro observations imply the potential for Kupffer cells to exert both stimulatory and inhibitory influences on hepatocyte DNA synthesis. We aimed to determine the overall effect of Kupffer cell activity during the early regenerative processes after partial hepatectomy. METHODS: We investigated hepatocyte DNA synthesis, induced by partial hepatectomy in rats, following selective elimination of Kupffer cells by liposome encapsulated dichlormethylene bisphosphonate (Cl2MBP). RESULTS: We demonstrate that the early phase of liver regeneration was enhanced following Kupffer depletion, as indicated by a greater proportion of hepatocytes undergoing DNA synthesis, and a higher mitotic index. This was associated with an alteration in the balance of growth factors in the liver; HGF and TGFbeta mRNA were reduced in Kupffer cell-depleted animals, and IL-1beta mRNA was absent. In addition, in the absence of partial hepatectomy, the selective depletion of Kupffer cells leads to an increase in the proliferation of hepatocytes in resting liver undergoing DNA synthesis. CONCLUSION: The overall effect of depleting the liver of Kupffer cells is to enhance the proliferation rate of hepatocytes, both after partial hepatectomy and in the resting state.
R A Boulton; M R Alison; M Golding; C Selden; H J Hodgson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  29     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-10-30     Completed Date:  1998-10-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  271-80     Citation Subset:  IM    
Department of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
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MeSH Terms
Cell Division
Clodronic Acid / administration & dosage,  toxicity
DNA / biosynthesis
Drug Carriers
Hepatocyte Growth Factor / biosynthesis,  genetics
Kupffer Cells / cytology,  drug effects,  physiology*
Liver / cytology*
Liver Regeneration / physiology*
Rats, Wistar
Transcription, Genetic / drug effects
Transforming Growth Factor beta / biosynthesis,  genetics
Reg. No./Substance:
0/Drug Carriers; 0/Liposomes; 0/Transforming Growth Factor beta; 10596-23-3/Clodronic Acid; 67256-21-7/Hepatocyte Growth Factor; 9007-49-2/DNA

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