RGD Reference Report - Tumor necrosis factor-alpha induces the aberrant expression of mucus core protein-2 in non-neoplastic biliary epithelial cells via the upregulation of CDX2 in chronic cholangitis. - Rat Genome Database

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Tumor necrosis factor-alpha induces the aberrant expression of mucus core protein-2 in non-neoplastic biliary epithelial cells via the upregulation of CDX2 in chronic cholangitis.

Authors: Ikeda, H  Sasaki, M  Ohira, S  Ishikawa, A  Sato, Y  Harada, K  Zen, Y  Nakanuma, Y 
Citation: Ikeda H, etal., Hepatol Res. 2008 Oct;38(10):1006-17. Epub 2008 May 27.
RGD ID: 2324885
Pubmed: PMID:18507686   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1872-034X.2008.00361.x   (Journal Full-text)

Aim: Chronic cholangitis, such as hepatolithiasis, is frequently associated with goblet cell metaplasia and the aberrant expression of mucus core protein-2 (MUC2). In this study, we clarified the role of inflammatory cytokines in the expression of MUC2 in lining biliary epithelial cells (BEC) in chronic cholangitis with an emphasis on CDX2, an intestine-specific transcription factor. Methods: We used human hepatolithiatic livers and polycystic kidney (PCK) rats, an animal model of Caroli's disease, and cultured BEC from PCK rats. As a control, extrahepatic biliary obstruction and histologically normal livers and Crj:CD rats were used. Results: Immunohistochemically, tumor necrosis factor-alpha (TNF-alpha) was expressed in periductal inflammatory cells and BEC of the affected intrahepatic bile ducts with an aberrant expression of MUC2 and CDX2 in hepatolithiasis and the PCK rats. In cultured BEC, TNF-alpha, interleukin (IL)-1beta, IL-6, and interferon-gamma induced the expression of CDX2 mRNA, though only TNF-alpha additionally induced the expression of MUC2 mRNA. The expression of CDX2 mRNA and the MUC2 protein induced in BEC by TNF-alpha were abolished by pretreatment of nuclear factor-kappaB inhibitors. Conclusion: The aberrant expression of CDX2 and MUC2 in the affected bile ducts showing goblet cell metaplasia was closely associated with TNF-alpha expressed in periductal infiltrating inflammatory cells and BEC. TNF-alpha induced the expression of CDX2 and MUC2 in cultured BEC. Taken together, it seems likely that TNF-alpha plays a role in MUC2 expression via CDX2 upregulation in the bile ducts with chronic cholangitis and goblet cell metaplasia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
primary biliary cholangitis  IEP 2324885 RGD 
primary biliary cholangitis  ISOMUC2 (Homo sapiens)2324885; 2324885 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to tumor necrosis factor  IEP 2324885 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Muc2  (mucin 2, oligomeric mucus/gel-forming)

Genes (Mus musculus)
Muc2  (mucin 2)

Genes (Homo sapiens)
MUC2  (mucin 2, oligomeric mucus/gel-forming)


Additional Information