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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，并进一步划分为各种成分不同的流体隔间。这种划分是由描绘体表和空洞的细胞上皮片建立的。为了使上皮细胞膜起到屏障的作用，必须对细胞旁途径中的溶质扩散有一定的封闭性。脊椎动物的紧密连接(TJ)被证明是造成这种细胞间密封的原因。最近发现的Claudins，一种与TJ屏障有关的细胞黏附分子，开辟了一种新的方法来扰乱单个隔室，并在整个身体水平上评估每个隔室的生理相关性。到目前为止，已在人/鼠中鉴定出24个claudin家族成员，据报道，这些成员以不同的组合和混合比例在单个细胞层中表达。已经证明，当小鼠体内构成其所描绘的上皮细胞层TJ的主要克拉丁物种的基因被纯合敲除时，特定的隔室可以被破坏。在这个项目中，我们培育并报道了claudin-1和claudin-5偏转小鼠。Claudin-1在表皮中大量表达，Claudin-1基因缺陷的小鼠表现出严重的表皮屏障功能障碍，出生后很快脱水。脑血管内皮细胞主要表达claudin-5，在claudin-5缺陷小鼠血脑屏障受到严重影响。现在我们可以讨论Claudins与脊椎动物的区域化之间的关系。

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）。