Analysis of biological function of tenascin-C in progression of heart failure and its clinical application

Tenascin-C在心力衰竭进展中的生物学功能分析及其临床应用

基本信息

批准号：
10670644
负责人：
IMAI Hiroshi
金额：
$ 2.43万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670644/
关键词：
Extracellular matrix tenascin myofibroblast knockout mouse myocardial infarction myocarditis 筋繊維芽細胞心疾患

项目摘要

In order to study the biological function, recombinant protein of tenascin-C was added to the cell cultures.1) Tenascin-C, collaborating with fibronectin, accelerates the initial attachment of cardiomyocytes isolated from adult rat to laminin, however, tenascin-C is not involved in the formation of costameric attachment. 2) Tenascin-C induces the differentiation of fibroblasts to myofibroblasts. Secondary, to clarify the role of tenascin-C if myocardial tissue in vivo, we examined the wound healing of a mouse myocardial infarction model using tenascin-C knockout mouse. In tenascin-C null mutant, the number of smooth-muscle actin-positive cells was delayed to compare to that of normal mouse, however, healing proceeded normally. Tenascin-X, another member of tenascin family was ubiquitously expressed in normal heart, and slightly unregulated after myocardial injury at later stage. Our findings did not suggested that tenascin-X compensates for the loss of tenascin-C. Finally, to examine the possibility of the clinical application anti tenascin-C, we have established a new autoimmune mouse model. We also raised a mouse monoclonal antibody, which recognizes mouse tenascin-C by immunization of a tenascin-C knock out mouse. Immunoshitological study showed that tenascin-C expressed at very early stage of active phase of myocarditis. Our data demonstrate that tenascin-C is a useful marker for histological diagnosis to evaluate disease activity of myocarditis.

为了研究生物学功能，将Tenascin-C的重组蛋白添加到细胞培养物中。1）Tenascin-C，与纤连蛋白合作，加速了从成年大鼠与层粘连蛋白分离的心肌细胞的初始附着，但是，Tenascin-C不涉及costameric colodameric coldameric coldameric coldameric contect。 2）Tenascin-C诱导成纤维细胞与肌纤维细胞的分化。继发性，为了阐明替纳斯蛋白-C如果体内心肌组织的作用，我们使用Tenascin-C基因敲除小鼠检查了小鼠心肌梗塞模型的伤口愈合。在Tenascin-C Null突变体中，平滑肌肉肌动蛋白阳性细胞的数量被延迟以与正常小鼠相比，愈合正常进行。 Tenascin-X是Tenascin家族的另一名成员，在正常的心脏中表达，在后期心肌损伤后略微不受管制。我们的发现并未提出Tenascin-X弥补了Tenascin-C的损失。最后，为了检查临床应用抗Tenascin-C的可能性，我们建立了一种新的自身免疫小鼠模型。我们还提出了一种小鼠单克隆抗体，该抗体通过对Tenascin-C敲出小鼠的免疫来识别小鼠Tenascin-C。免疫学研究表明，在心肌炎的活性期很早的阶段表达了Tenascin-C。我们的数据表明，Tenascin-C是组织学诊断以评估心肌炎疾病活性的有用标记。