Tight Junctions in Normal and Cholestatic Liver: Does the Paracellular Pathway Have Functional Significance?

Tight Junctions in Normal and Cholestatic Liver: Does the Paracellular Pathway Have Functional Significance?
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正常肝脏和胆汁淤积肝脏中的紧密连接:细胞旁通路是否具有功能意义?

DOI:
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发表时间:
2007
期刊:
影响因子:
13.5
通讯作者:
J. Boyer
J. Boyer
中科院分区:
医学1区
文献类型:
--
作者:
J. Boyer

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Tight junctions (zonulae occludens) seal the lumen of bile canaliculi between adjacent hepatocytes, defining the size of the canaliculus and providing a barrier to diffusion between blood and bile. Thus, they are strategically situated to influence the formation of bile and the pathogenesis of cholestasis. Evidence from physiologic and anatomical studies suggests that these junctions have selective permeability for fluid and certain solutes, and that their structure and permeability are disturbed in experimental models of cholestasis and obstructive jaundice in man (1-3). Since the endothelial lining of the hepatocyte sinusoid is highly fenestrated, blood plasma is in diffusion equilibrium with the intercellular space. Therefore, the tight junction is the major anatomical barrier to diffusion between blood and bile which, by analogy to epithelial tissues, should be capable of regulating permeability between them. As eloquently discussed by Diamond, tight junctions or “kisses in the dark” function in epithelial tissues as bridges, fences, or gates. (4). It is not known whether liver cell tight junctions serve a bridging function although it is possible that they maintain electrical contact between hepatocytes in pathologic situations such as liver regeneration where gap junctions, the traditional conducts of electrical contact, are lost (5). Instead, the major function of liver cell tight junctions seems to be to maintain a permeability seal between adjacent hepatocytes thus both delineating the canalicular lumen and selectively retaining the bile content within it.