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Claudins in the epithelium/endothelium barrier dysfucrition

上皮/内皮屏障功能障碍中的 Claudins

基本信息

批准号：
14207008
负责人：
TSUKITA Shoichiro
金额：
$ 30.45万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

In multicellular organisms, the internal environment must be isolated and buffered against the external environment, and further divided into various compositionally distinct fluid compartments. This compartmentalization is established by cellular sheets of epithelia delineating the body surface and cavities. For epithelial cellular sheets to function as barriers, there must be some seal to the diffusion of solutes through the paracellular pathway. Tight junctions(TJs) have teen shown to be responsible for this intercellular sealing in vertebrates. Recent identification of claudins, cell adhesion molecules responsible for the TJ barrier, opened a new way to perturb individual compartments, and to evaluate the physiological relevance of each compartment at a whole body level. To date, 24 members of the claudin family have been identified in human/mouse, and these are reported to be expressed in individual cell layers in various combinations and mixing ratios. It has been shown that a particular compartment can be destroyed, when the gene for major species of claudins constituting TJs of its delineating epithelial cell layer is homozygously knocked out in mice. In this project, we generated and reported claudin-1-and claudin-5-deflcient mice. Claudin-1 is expressed in large amounts in the epidermis, and claudin-1-deficient mice showed severe dysfunction of the epidermal barrier, being dehydrated quickly after birth. Endothelial cells of brain blood vessels primarily express claudin-5, and in claudin-5-deficient mice, the blood-brain barrier was severely affected. Now we can discuss the relationship of claudins with the compartmentalization in vertebrates.

在多细胞生物中，内部环境必须与外部环境隔离和缓冲，并进一步分为各种成分不同的流体室。这种区室化是由描绘身体表面和空腔的上皮细胞片层建立的。为了使上皮细胞片层发挥屏障作用，必须对溶质通过细胞旁途径的扩散进行某种密封。研究表明，紧密连接 (TJ) 负责脊椎动物的细胞间密封。最近对紧密蛋白（负责 TJ 屏障的细胞粘附分子）的鉴定，开辟了一种扰动各个隔室并在全身水平评估每个隔室的生理相关性的新方法。迄今为止，已在人类/小鼠中鉴定出密蛋白家族的 24 个成员，据报道这些成员以各种组合和混合比例在各个细胞层中表达。已经表明，当在小鼠中纯合地敲除构成其描绘的上皮细胞层的TJ的主要密蛋白种类的基因时，特定的区室可以被破坏。在这个项目中，我们生成并报告了claudin-1和claudin-5缺陷的小鼠。 Claudin-1在表皮大量表达，claudin-1缺陷的小鼠表现出严重的表皮屏障功能障碍，出生后迅速脱水。脑血管内皮细胞主要表达claudin-5，在claudin-5缺陷的小鼠中，血脑屏障受到严重影响。现在我们可以讨论紧密蛋白与脊椎动物区室化的关系。

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Achlorhydria by ezrin knockdown: defects in the formation/expansion of apical canaliculi in gastric parietal cells.

DOI：
10.1083/jcb.200410083
发表时间：
2005-04-11
期刊：
The Journal of cell biology
影响因子：
0
作者：
Tamura A;Kikuchi S;Hata M;Katsuno T;Matsui T;Hayashi H;Suzuki Y;Noda T;Tsukita S;Tsukita S
通讯作者：
Tsukita S

Claudins in Caenorhabditis elegans:: Their distribution and barrier function in the epithelium

DOI：
10.1016/s0960-9822(03)00395-6
发表时间：
2003-06-17
期刊：
CURRENT BIOLOGY
影响因子：
9.2
作者：
Asano, A;Asano, K;Tsukita, S
通讯作者：
Tsukita, S

Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

DOI：
10.1083/jcb.200501154
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
0
作者：
Miyamoto T;Morita K;Takemoto D;Takeuchi K;Kitano Y;Miyakawa T;Nakayama K;Okamura Y;Sasaki H;Miyachi Y;Furuse M;Tsukita S
通讯作者：
Tsukita S

Dynamic behavior of paired claudin strands within apposing plasma membranes

DOI：
10.1073/pnas.0630649100
发表时间：
2003-04-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Sasaki, H;Matsui, C;Tsukita, S
通讯作者：
Tsukita, S

Matsuda, M.et al.: "A peculiar interaalization of claudins, tight junction -specific adhesion molecules, during the intercellular movement of epithelial cells"J.Cell Sci.. 印刷中. (2004)

Matsuda, M. 等人：“在上皮细胞的细胞间运动过程中紧密连接特异性粘附分子的特殊内化”J.Cell Sci.. 出版中（2004 年）。