RGD Reference Report - RNA interference against hepatic epidermal growth factor receptor has suppressive effects on liver regeneration in rats. - Rat Genome Database

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RNA interference against hepatic epidermal growth factor receptor has suppressive effects on liver regeneration in rats.

Authors: Paranjpe, Shirish  Bowen, William C  Tseng, George C  Luo, Jian-Hua  Orr, Anne  Michalopoulos, George K 
Citation: Paranjpe S, etal., Am J Pathol. 2010 Jun;176(6):2669-81. doi: 10.2353/ajpath.2010.090605. Epub 2010 Apr 15.
RGD ID: 38599218
Pubmed: PMID:20395437   (View Abstract at PubMed)
PMCID: PMC2877830   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2010.090605   (Journal Full-text)

Liver regeneration after a two-thirds partial hepatectomy (PHx) is a complex process requiring interaction and cooperation of many growth factors and cytokines and cross talk between multiple pathways. Along with hepatocyte growth factor and its receptor MET (HGF-MET), the epidermal growth factor receptor (EGFR) signaling pathway is activated within 60 minutes after PHx. To investigate the role of EGFR in liver regeneration, we used two EGFR-specific short hairpin silencing RNAs to inhibit EGFR expression in regenerating normal rat liver. Suppression of EGFR mRNA and protein was evident in treated rats. There was also a demonstrable decrease but not complete elimination of bromo-deoxyuridine incorporation and mitoses at 24 hours after PHx. In addition, we observed up-regulation of MET and Src as well as activation of the ErbB-3-ErbB-2-PI3K-Akt pathway and down-regulation of STAT 3, cyclin D1, cyclin E1, p21, and C/EBP beta. The decrease in the ratio of C/EBP alpha to C/EBP beta known to occur after PHx was offset in shEGFR-treated rats. Despite suppression of hepatocyte proliferation lasting into day 3 after PHx, liver weight restoration occurred. Interestingly, hepatocytes in shEGFR-treated rats were considerably larger when compared with ScrRNA-treated controls. The data indicate that although the MET and EGFR pathways are similar, the contributions made by MET and EGFR are unique and are not compensated by each other or other cytokines.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver regeneration  IMP 38599218 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)


Additional Information