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

基于间隙连接细胞内通讯四维分析的病理学分析及其治疗发展

• 批准号: 17209058
• 负责人: MORITA Ikuo
• 金额: $ 32.12万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17209058/
• 关键词: Connexin; Gap Junction; Differentiation; Cell Density; Expression; mRNA Stability; PI3 kinase; 発現調節; mRNA安定性; 骨代謝; DDS; 細胞増殖

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

Cx43在细胞增殖、分化和凋亡中起着多种作用。为了确定Cx43是否有助于细胞分化，我们首先表征了Cx43在细胞分化过程中的表达。目前的研究表明，在肝细胞中，Cx43的表达上调与癌变，维生素K2衰减癌细胞增殖和刺激细胞分化的抑制Cx43的表达，Cx43是至关重要的体外RPE细胞分化。Cx43短发夹状RNA显著抑制RPE细胞分化，而Cx43过表达促进RPE细胞分化，并且Cx43对RPE细胞分化的调控是通过cAMP的积累而不是通过细胞间缝隙连接通讯（GJIC）实现的。除了膜运输的连接蛋白（Cx）蛋白，我们专注于Cx43的基因表达的调控。高细胞密度时Cx43的表达增强与细胞内间隙功能无关。 ...更多信息 细胞间的间隙连接。但细胞间的差距连接影响了cx43的膜转运。高浓度诱导的Cx43基因表达上调可被Cx43启动子区的SP1结合基序所阻断，而SP3的下调则有助于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的稳定性。我们还研究了各种连接蛋白的表达模式和Cx在细胞分化中的作用。我们建立了牙周膜组织中多能干细胞的分离及向成骨细胞的分化、脐带血内皮细胞的分化和视网膜色素上皮细胞的分化等细胞分化体系。有趣的是，Cx43的表达在所有检测的系统中均被细胞分化上调，并且Cx43通过间隙连接非依赖性方式参与细胞分化。少

项目成果

Connexin 43 expression is up-regulated by gap junction-independent cell-cell contact

Connexin 43 表达通过间隙连接独立的细胞间接触上调

• 发表时间: 2007
• 作者: Makoto Kaneda;Bhattacharjee Rajib;Ken-ichi Nakahama;Ikuo MoritaYokohama
• 通讯作者: Ikuo MoritaYokohama

Expression and possible role of PVR/CD155/Necl-5 in osteoclastogenesis

• DOI: 10.1007/s11010-007-9413-x
• 发表时间: 2007-07-01
• 期刊: MOLECULAR AND CELLULAR BIOCHEMISTRY
• 影响因子: 4.3
• 作者: Kakehi, Saori;Nakahama, Ken-ichi;Morita, Ikuo
• 通讯作者: Morita, Ikuo

Connexin 43 expression promotes malignancy of HuH7 hepatocellular carcinoma cells via the inhibition of cell-cell communication

• DOI: 10.1016/j.canlet.2006.12.024
• 发表时间: 2007-07-18
• 期刊: CANCER LETTERS
• 影响因子: 9.7
• 作者: Zhang, Dan;Kaneda, Makoto;Morita, Ikuo
• 通讯作者: Morita, Ikuo

The effects of amniotic membrane on retinal pigment epithelial cell differentiation.

• 发表时间: 2005-01
• 期刊: Molecular vision
• 影响因子: 2.2
• 作者: K. Ohno-Matsui;S. Ichinose;K. Nakahama;Takeshi Yoshida;A. Kojima;M. Mochizuki;I. Morita

印刷技術を用いて作成した毛細血管のin vitro及びin vivoにおける評価

使用打印技术创建的毛细血管的体外和体内评估

• 发表时间: 2007
• 作者: 赤堀太一;向井奈々;小牧基浩;安部まゆみ;竹田 省;森田育男
• 通讯作者: 森田育男