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

1）Tenascin-C与纤连蛋白（FN）协同作用，促进大鼠心肌细胞与层粘连蛋白（LN）的初始粘附，但不参与肋膜粘附的形成。2)生腱蛋白-C诱导成纤维细胞分化为肌成纤维细胞。其次，为了阐明生腱蛋白-C在体内心肌组织中的作用，我们使用生腱蛋白-C敲除小鼠检查了小鼠心肌梗死模型的伤口愈合。在腱生蛋白-C无效突变体中，平滑肌肌动蛋白阳性细胞的数量与正常小鼠相比延迟，然而，愈合正常进行。腱生蛋白家族的另一个成员腱生蛋白-X在正常心脏中广泛表达，在心肌损伤后期表达略有失调。我们的研究结果并没有表明腱生蛋白-X补偿了腱生蛋白-C的损失。最后，为了验证抗腱生蛋白C在临床上应用的可能性，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，其识别小鼠腱生蛋白-C的免疫小鼠腱生蛋白-C敲除小鼠。免疫组化结果显示腱生蛋白C在心肌炎活动期的极早期即有表达。我们的数据表明，腱生蛋白-C是一个有用的组织学诊断指标，以评估疾病的活动性心肌炎。

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.