Analysis of pathology based on four-dimensional analysis of intracellular communication through gap junction and their development for therapy

Cx43在细胞增殖、分化和凋亡中发挥多种作用。为了确定Cx43是否有助于细胞分化，我们首先表征了细胞分化过程中Cx43的表达。本研究表明，在肝细胞中，Cx43的表达随着癌的发生而上调，维生素K2通过抑制Cx43的表达来减弱癌细胞的增殖并刺激细胞分化，而Cx43在体外对RPE细胞的分化至关重要。Cx43短发夹RNA显著抑制RPE细胞分化，而Cx43过表达促进RPE细胞分化。此外，Cx43对RPE细胞分化的调节来自cAMP的积累，而不是来自细胞间隙连接通讯（GJIC）。除了连接蛋白（Cx）的膜运输外，我们还关注了Cx43基因表达的调控。高细胞密度下Cx43的表达增强与细胞内间隙功能无关，细胞间有更多的通讯和间隙连接。然而，cx43的膜运输受到细胞间间隙连接的影响。高密度上调的Cx43的表达被Cx43启动子区SP1结合基序所消除，Sp3的下调将促进Cx43基因表达的上调。此外，Cx43基因的表达也受到mRNA稳定化的调控。PI3激酶和AKT均影响Cx43 mRNA的稳定。我们还研究了各种连接蛋白的表达模式以及Cx在细胞分化中的作用。我们建立了细胞分化系统；从牙周韧带组织中分离多能干细胞并向成骨细胞、脐带血内皮细胞和视网膜色素上皮细胞分化。有趣的是，在所研究的所有系统中，Cx43的表达都随着细胞分化而上调，并且Cx43通过不依赖于间隙连接的方式参与细胞分化。少

Cx43 plays various roles in cell proliferation, differentiation, and apoptosis. To ascertain whether Cx43 contributes to cell differentiation, we initially characterized Cx43 expression during cell differentiation. The present study shows that in hepatocytes, Cx43 expression is upregulated with carcinogenesis, and vitamin K2 attenuated cancer cell proliferation and stimulated cell differentiation by the suppression of Cx43 expression, and Cx43 is crucial for RPE cell differentiation in vitro. Cx43 short hairpin RNA dramatically inhibited RPE cell differentiation, whereas Cx43 overexpression facilitated it. Furthermore, the regulation of RPE cell differentiation by Cx43 results from the accumulation of cAMP, not from intercellular gap junctional communication (GJIC). In addition to membrane trafficking of connexin (Cx) protein, we focused on the regulation of gene expression of Cx43. The enhanced expression of Cx43 with high cell density was independent of gap functional intracellular c … More ommunication and gap junction between cells. However, the membrane trafficking of cx43 was affected with the gap junction between cells. The expression of Cx43 upregulated by high density was abolished by SP1 binding motif in Cx43 promoter region and Sp3 down-regulation will contribute the upregulation of cx43 gene expreswsion. Moreover, the Cx43 gene expression was also regulated by mRNA stabilization. Both PI3 kinase and AKT affected mRNA stabilization of Cx43. We also examined the expression pattern of various connexins and the role of Cx in cell differentiation. We have established the cell differentiation systems; isolation of multi potent stem cells from periodontal ligament tissues and differentiation to osteoblasts, endothelial cell differentiation from cord blood and differentiation of retina pigmental epithelia cells. It is interesting that Cx43 expression was upregulated by cell differentiation in all systems examined and Cx43 involves in cell differentiation via gap junction-independent manner. Less