Kojima Takashi, Murata Masaki, Go Mitsuru, Spray David C, Sawada Norimasa
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Membr Biol. 2007 Jun;217(1-3):13-9. doi: 10.1007/s00232-007-9021-4. Epub 2007 Jun 14.
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.
连接蛋白（Cx）被认为在上皮细胞分化中起关键作用，并与黏着连接和紧密连接相关。本综述描述了连接蛋白如何促进上皮细胞、肝细胞和气道上皮细胞中紧密连接的诱导和维持。内源性Cx32表达和介导的细胞间通讯与原代培养大鼠肝细胞紧密连接蛋白的表达有关。我们将人Cx32基因导入源自Cx32缺陷小鼠的永生化小鼠肝细胞中。外源性Cx32表达和转染介导的细胞间通讯可诱导紧密连接的表达和功能。转染还诱导了MAGI-1的表达，其以不依赖缝隙连接细胞间通讯（GJIC）的方式定位于黏着连接和紧密连接区域。此外，Cx32的表达与肝细胞单个上皮细胞极性的形成有关。另一方面，Cx26表达而非介导的细胞间通讯有助于人气道上皮细胞中紧密连接的表达和功能。我们将人Cx26基因导入人气道上皮细胞系Calu-3，并使用Na(+)/K(+)-ATP酶抑制剂哇巴因破坏紧密连接的模型。用Cx26转染可防止哇巴因处理导致的紧密连接功能（屏障和栅栏功能）破坏以及紧密连接蛋白的变化，且这种作用不依赖GJIC。这些结果表明，连接蛋白可以通过依赖GJIC和不依赖GJIC的方式在上皮细胞中诱导和维持紧密连接。
