RGD Reference Report - Combined Stimulation with the Tumor Necrosis Factor alpha and the Epidermal Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured Slices. - Rat Genome Database

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Combined Stimulation with the Tumor Necrosis Factor alpha and the Epidermal Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured Slices.

Authors: Finot, F  Masson, R  Desmots, F  Ribault, C  Bichet, N  Vericat, JA  Lafouge, P  Guguen-Guillouzo, C  Loyer, P 
Citation: Finot F, etal., Int J Hepatol. 2012;2012:785786. doi: 10.1155/2012/785786. Epub 2012 Oct 16.
RGD ID: 7207882
Pubmed: PMID:23119170   (View Abstract at PubMed)
PMCID: PMC3480011   (View Article at PubMed Central)
DOI: DOI:10.1155/2012/785786   (Journal Full-text)

The culture liver slices are mainly used to investigate drug metabolism and xenobiotic-mediated liver injuries while apoptosis and proliferation remain unexplored in this culture model. Here, we show a transient increase in LDH release and caspase activities indicating an ischemic injury during the slicing procedure. Then, caspase activities decrease and remain low in cultured slices demonstrating a low level of apoptosis. The slicing procedure is also associated with the G0/G1 transition of hepatocytes demonstrated by the activation of stress and proliferation signalling pathways including the ERK1/2 and JNK1/2/3 MAPKinases and the transient upregulation of c-fos. The cells further progress up to mid-G1 phase as indicated by the sequential induction of c-myc and p53 mRNA levels after the slicing procedure and at 24 h of culture, respectively. The stimulation by epidermal growth factor induces the ERK1/2 phosphorylation but fails to activate expression of late G1 and S phase markers such as cyclin D1 and Cdk1 indicating that hepatocytes are arrested in mid-G1 phase of the cell cycle. However, we found that combined stimulation by the proinflammatory cytokine tumor necrosis factor alpha and the epidermal growth factor promotes the commitment to DNA replication as observed in vivo during the liver regeneration.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MycRatG0 to G1 transition  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myc  (MYC proto-oncogene, bHLH transcription factor)


Additional Information