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Role of the claudin tight junction protein in tube formation during mammalian organ development

紧密连接蛋白在哺乳动物器官发育过程中管形成中的作用

基本信息

批准号：
17570178
负责人：
HIEDA Yohki
金额：
$ 2.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Research on the tube formation in developing organs of mammals was made using the mouse submandibular gland as a model system. The investigator has obtained the results described below.(1) The expression pattern of major tight junction proteins, including ZO-1, occludin and claudins, was examined in developing submandibular gland. It turned out that ZO-1 expression was followed by occludin and then by claudins. These tight junction proteins were expressed in a dot-like manner before the beginning of tube formation and then gradually in a thin and linear pattern typical of the tight junction distribution as tube formation proceeds.(2) Certain members of the claudin family specifically bind to a bacterial peptide toxin (C-CPE) and the binding of C-CPE causes downregulation of claudin expression. To investigate the role of claudins in tube formation, developing submandibular glands were cultured in the presence of C-CPE. Claudin expression and tube formation were inhibited in the treated glands but not the control glands, indicating the involvement of claudins in tube formation.(3) The investigator previously showed in an organ culture of the mouse submandibular gland that epithelial tube formation and cell polarization, including tight junction formation, in the developing gland was promoted in the presence of a biologically active peptide fragment of the Sonic hedgehog (Shh) signaling molecule. In the present study the investigator have revealed that in addition to Shh, two other members of the hedgehog family, Indian hedgehog (Ihh) and Desert hedgehog (Dhh), are expressed in developing submandibular gland of mouse. Furthermore, the investigator has found that Ihh peptide promotes epithelial tube formation and cell polarization more efficiently than Shh peptide. (paper in preparation)

以小鼠颌下腺为模型系统，对哺乳动物器官发育过程中管状结构的形成进行了研究。研究者获得了下述结果。(1)主要紧密连接蛋白，包括ZO-1，occludin和claudins，在发育中的下颌下腺的表达模式进行了检查。结果表明，ZO-1表达后是闭合蛋白，然后是封闭蛋白。这些紧密连接蛋白在管形成开始之前以点状方式表达，然后随着管形成的进行逐渐以典型的紧密连接分布的薄且线性的模式表达。(2)紧密连接蛋白家族的某些成员特异性结合细菌肽毒素（C-CPE），并且C-CPE的结合导致紧密连接蛋白表达的下调。为了研究claudins在管形成中的作用，在C-CPE存在下培养发育中的下颌下腺。封闭蛋白的表达和管的形成被抑制在治疗的腺体，但不控制腺体，表明在管的形成中的封闭蛋白的参与。(3)研究人员先前在小鼠下颌下腺的器官培养中显示，在Sonic hedgehog（Shh）信号分子的生物活性肽片段存在下，促进了发育中腺体中上皮管形成和细胞极化，包括紧密连接形成。在本研究中，研究人员发现，除了Shh，刺猬家族的另外两个成员，印度刺猬（Ihh）和沙漠刺猬（Dhh），在发育中的小鼠下颌下腺中表达。此外，研究者发现Ihh肽比Shh肽更有效地促进上皮管形成和细胞极化。（文件正在编写中）