Connexins Induce and Maintain Tight Junctions in Epithelial Cells |
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Authors: | Takashi Kojima Masaki Murata Mitsuru Go David C Spray Norimasa Sawada |
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Institution: | (1) Department of Pathology, Sapporo Medical University School of Medicine, S1 W17, Sapporo 060-8556, Japan;(2) Department of Otolaryngology, Sapporo Medical University School of Medicine, S1 W17, Sapporo 060-8556, Japan;(3) Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA |
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Abstract: | Connexins (Cx) are considered to play a crucial role in the differentiation of epithelial cells and to be associated with
adherens and tight junctions. This review describes how connexins contribute to the induction and maintenance of tight junctions
in epithelial cells, hepatic cells and airway epithelial cells. Endogenous Cx32 expression and mediated intercellular communication
are associated with the expression of tight junction proteins of primary cultured rat hepatocytes. We introduced the human
Cx32 gene into immortalized mouse hepatic cells derived from Cx32-deficient mice. Exogenous Cx32 expression and the mediated
intercellular communication by transfection could induce the expression and function of tight junctions. Transfection also
induced expression of MAGI-1, which localized at adherens and tight junction areas in a gap junctional intercellular communication
(GJIC)–independent manner. Furthermore, expression of Cx32 was related to the formation of single epithelial cell polarity
of the hepatic cells. On the other hand, Cx26 expression, but not mediated intercellular communication, contributed to the
expression and function of tight junctions in human airway epithelial cells. We introduced the human Cx26 gene into the human
airway epithelial cell line Calu-3 and used a model of tight junction disruption by the Na+/K+-ATPase inhibitor ouabain. Transfection with Cx26 prevented disruption of both tight junction functions, the fence and barrier,
and the changes of tight junction proteins by treatment with ouabain in a GJIC–independent manner. These results suggest that
connexins can induce and maintain tight junctions in both GJIC-dependent and –independent manners in epithelial cells. |
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Keywords: | Connexin Gap junction Tight junction Hepatocyte Airway epithelial cell Fence function Barrier function Protein-protein interaction |
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