Studies of barrier function of tight junction in epithelial celllayers and strategic development of novel methods for drug permeation enhancement in cells
上皮细胞层紧密连接屏障功能的研究和细胞内药物渗透增强新方法的战略开发
基本信息
- 批准号:21590178
- 负责人:
- 金额:$ 2.91万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2009
- 资助国家:日本
- 起止时间:2009 至 2011
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The aim of this study was to evaluate the barrier function of tight junction(TJ) in epithelial cell layers and to develop novel methods for drug permeation enhancement in cells.We investigated the expression profiles of gene and the changes in gene expression in Caco-2 cells, when the C-terminal fragment of Clostridium perfringens enterotoxin(C-CPE), a permeation enhancement modulator targeted to claudins playing a pivotal role in the barrier function of TJ, was applied in cell monolayers. The formation of TJ barriers in Caco-2 monolayers was monitored by the transepithelial resistance(TER) assay. We investigated approximately 45, 000 genes. The expression of 106 genes was increased in 4 times, whereas the expression of 182 genes was decreased in 1/4, when TJ barrier function was decreased by the treatment of C-CPE.We focused the macropinocytosis induced by adenovirus(Ad) vector for drug delivery, because macropinocytosis can be used delivery of macromolecules, nanoparticles, and so on. It was found that macropinocytosis induced by the fiber shaft protein of Ad type 35(Ad35 Shaft) can be delivered a model of macromolecular drug, FITC-dextran(M. W. 40, 000) in HepG2 cells. Also, we observed the Ad35 Shaft-mediated gene expression of plasmid transduction into HepG2 cells. These results suggested that the fiber shaft protein, especially Ad35 Shaft, is a useful tool for the systems of macromolecular drug therapy and gene delivery into cells.
本研究的目的是评估上皮细胞层紧密连接(TJ)的屏障功能,并开发增强细胞内药物渗透的新方法。我们研究了产气荚膜梭菌肠毒素(Clostridium perfringens enterotoxin, C-CPE)的c端片段在Caco-2细胞中的表达谱和表达变化,C-CPE是一种针对在TJ屏障功能中起关键作用的cladin的渗透增强调节剂。通过经上皮耐药(TER)试验监测Caco-2单层膜中TJ屏障的形成。我们调查了大约45000个基因。当C-CPE治疗降低TJ屏障功能时,106个基因的表达量增加了4倍,182个基因的表达量减少了1/4。我们关注腺病毒(Ad)载体诱导的巨噬细胞作用用于药物递送,因为巨噬细胞作用可以用于大分子、纳米颗粒等的递送。发现由Ad35型纤维轴蛋白(Ad35 shaft)诱导的巨量红细胞增生可以传递一种大分子药物fitc -葡聚糖(M。W. 40000)在HepG2细胞中。此外,我们观察到Ad35轴介导的基因表达质粒转导到HepG2细胞。这些结果表明,纤维轴蛋白,特别是Ad35轴蛋白,是大分子药物治疗和基因传递系统的有用工具。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Development of a novel therapeutic system of adenovirus gene therapy in combination of macromolecular drug therapy
腺病毒基因治疗联合大分子药物治疗的新型治疗体系的开发
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Y.Watanabe;N.Koizumi;Y.Yamagishi;E;Hagiwara;H.Mizuguchi;M.Fujii
- 通讯作者:M.Fujii
アデノウイルス由来Shaft質による物質取り込み機構の解明
阐明腺病毒衍生轴物质的物质摄取机制
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:山岸喜彰;酒井宏;小泉直也;藤井まき子;水口裕之;渡辺善照
- 通讯作者:渡辺善照
タイトジャンクションバリアー機能に関与する遺伝子の解析
紧密连接屏障功能相关基因分析
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:鷲山真紀子;小泉直也;苅込亜美;佐々木杏沙;松本有未;藤井まき子;近藤昌夫;八木清仁;渡辺善照
- 通讯作者:渡辺善照
MDCK細胞におけるタイトジャンクション機能へのSec61b遺伝子の関与
Sec61b基因参与MDCK细胞紧密连接功能
- DOI:
- 发表时间:2012
- 期刊:
- 影响因子:0
- 作者:鷲山真紀子;小泉直也;佐々木杏沙;松本有未;藤井まき子;近藤昌夫;八木清仁;渡辺善照
- 通讯作者:渡辺善照
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
WATANABE Yoshiteru其他文献
WATANABE Yoshiteru的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('WATANABE Yoshiteru', 18)}}的其他基金
Strategic approach based on molecular mechanism for modulation of barrier function of tight junction to enhance delivery of new biopharmaceuticals
基于分子机制调节紧密连接屏障功能以增强新生物药物递送的战略方法
- 批准号:
25460222 - 财政年份:2013
- 资助金额:
$ 2.91万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A Novel Strategy for Enhancement of Permeation and Absorption of Drugs by Modulation of Proteins Constructed Barrier Function in Biomembrane
通过调节生物膜中蛋白质构建的屏障功能来增强药物渗透和吸收的新策略
- 批准号:
19590159 - 财政年份:2007
- 资助金额:
$ 2.91万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies on Drug Permeation in Placental Barrier by RNA Interference
RNA干扰药物在胎盘屏障渗透的研究
- 批准号:
17590136 - 财政年份:2005
- 资助金额:
$ 2.91万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of Gene Transfer Systems into Placental Cells for Studies of Drug Transport Mechanism in Blood-Placenta Barrier
开发胎盘细胞基因转移系统以研究血胎盘屏障中的药物转运机制
- 批准号:
15590139 - 财政年份:2003
- 资助金额:
$ 2.91万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies on the development of new drug adsorption-enhancing systems based on physiological action of nitric oxide (NO)
基于一氧化氮(NO)生理作用的新型药物吸附增强系统开发研究
- 批准号:
10672092 - 财政年份:1998
- 资助金额:
$ 2.91万 - 项目类别:
Grant-in-Aid for Scientific Research (C)