Histochemistry and Cell Biology

, Volume 129, Issue 3, pp 289–299 | Cite as

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

  • I. Piotr Maly
  • Lukas Landmann
Original Paper


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.


Bile secretion Cholestasis Tight junctions Hepatocytes Transepithelial permeability 



Tight junctions




Bile duct ligation


Release of ligation


Alkaline phosphatase



We thank Mireille Toranelli, Petra Banse and Jean Paul Boeglin for expert technical assistance.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of AnatomyUniversity of BaselBaselSwitzerland
  2. 2.Structural Cell Biology, DKBW Centre for BiomedicineUniversity of Basel Medical SchoolBaselSwitzerland

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