RGD Reference Report - Bile duct ligation in the rat causes upregulation of ZO-2 and decreased colocalization of claudins with ZO-1 and occludin. - Rat Genome Database

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Bile duct ligation in the rat causes upregulation of ZO-2 and decreased colocalization of claudins with ZO-1 and occludin.

Authors: Maly, IP  Landmann, L 
Citation: Maly IP and Landmann L, Histochem Cell Biol. 2008 Mar;129(3):289-99. Epub 2008 Jan 15.
RGD ID: 2325141
Pubmed: PMID:18197414   (View Abstract at PubMed)
DOI: DOI:10.1007/s00418-007-0374-7   (Journal Full-text)

As the only barrier between blood and bile compartments hepatocellular tight junctions play a crucial role in cholestasis-induced increase of biliary permeability. The molecular basis of this reversible defect is not known. We, therefore, examined expression, phosphorylation, distribution and colocalization of the junctional proteins occludin, claudin-1-3, ZO-1 and ZO-2 in rats after bile duct ligation and release of ligation. In control rats, claudin-1 and ZO-2 displayed a lobular gradient with highest expression levels in periportal cells, whereas claudin-2 showed a reciprocal distribution. Other proteins were evenly expressed in the liver lobule. Ligation resulted in upregulation of ZO-2 (2.7-fold), ZO-1 (1.4-fold) and occludin (1.2-fold) but not of claudins. Only ZO-2 showed increased phosphorylation. Distribution patterns were unchanged except for a strong accumulation of ZO-2 in perivenous hepatocytes. Colocalization analysis demonstrated that perivenous ZO-2 was the only protein examined revealing strongly increased overlap with occludin and ZO-1, whereas claudins and other proteins displayed a decrease. All changes were partially reversed by release of ligation. We conclude that differential expression of claudin-1-2 and ZO-2 has functional implications for bile formation. The moderately increased ZO-1 and occludin levels account for the known elongation of tight junction strands. The highly increased expression and changed distribution of ZO-2 suggests that ZO-1 is partly substituted by ZO-2, an alteration possibly causing impaired barrier function.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TJP1Humancholestasis  ISOTjp1 (Rattus norvegicus)protein:increased expression:liverRGD 
Tjp1Ratcholestasis  IEP protein:increased expression:liverRGD 
Tjp1Mousecholestasis  ISOTjp1 (Rattus norvegicus)protein:increased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tjp1  (tight junction protein 1)

Genes (Mus musculus)
Tjp1  (tight junction protein 1)

Genes (Homo sapiens)
TJP1  (tight junction protein 1)


Additional Information