RGD Reference Report - Expression of the Notch signaling pathway and effect on exocrine cell proliferation in adult rat pancreas. - Rat Genome Database

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Expression of the Notch signaling pathway and effect on exocrine cell proliferation in adult rat pancreas.

Authors: Rooman, I  De Medts, N  Baeyens, L  Lardon, J  De Breuck, S  Heimberg, H  Bouwens, L 
Citation: Rooman I, etal., Am J Pathol. 2006 Oct;169(4):1206-14.
RGD ID: 2311231
Pubmed: PMID:17003479   (View Abstract at PubMed)
PMCID: PMC1698841   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2006.050926   (Journal Full-text)

When pancreatic tissue is injured after duct obstruction, acinoductal metaplasia is observed. Similar metaplastic changes occur when exocrine pancreatic cells are isolated and cultured. We demonstrate that under these experimental conditions the exocrine acinar cells lose their differentiated characteristics: expression of the acinar transcription factors p48/Ptf1alpha and Mist1 is decreased or lost, whereas expression of the embryonic transcription factor Pdx1 is increased. The receptors Notch1 and Notch2, members of the DSL family of Notch ligands, and the target genes in the Notch-signaling pathway Hes1, Hey1, and Hey2 become strongly up-regulated. We noted also reduced expression of Sel1L, a Notch repressor that is normally highly expressed in exocrine pancreas. Stimulation of Notch by its ligand Jagged1 diminished the proliferation of cultured metaplastic exocrine cells. Chemical inhibition of Notch signaling resulted in increased proliferation and induction of the cell-cycle regulator p21Cip1. This effect seems to be Hes1-independent and mainly coincides with decreased Hey1 and Hey2 mRNA expression. In conclusion, we demonstrate that during acinoductal metaplasia the Notch-signaling pathway is activated concomitantly with changes in transcription factor expression of pancreatic acinar cells. In addition, we show that Notch signaling is implicated in the suppression of proliferation of these metaplastic exocrine cells. The latter may be important in protection from neoplastic transformation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDX1HumanMetaplasia  ISOPdx1 (Rattus norvegicus)mRNA and protein:increased expression:pancreatic acinus (rat)RGD 
Pdx1RatMetaplasia  IEP mRNA and protein:increased expression:pancreatic acinus (rat)RGD 
Pdx1MouseMetaplasia  ISOPdx1 (Rattus norvegicus)mRNA and protein:increased expression:pancreatic acinus (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Mus musculus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Homo sapiens)
PDX1  (pancreatic and duodenal homeobox 1)


Additional Information