Bile duct ligation in the rat causes upregulation of ZO-2 and decreased colocalization of claudins with ZO-1 and occludin |
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Authors: | I Piotr Maly Lukas Landmann |
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Institution: | (1) Department of Anatomy, University of Basel, Basel, Switzerland;(2) Structural Cell Biology, DKBW Centre for Biomedicine, University of Basel Medical School, Mattenstrasse 28, 4058 Basel, Switzerland |
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Abstract: | 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. |
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Keywords: | Bile secretion Cholestasis Tight junctions Hepatocytes Transepithelial permeability |
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