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

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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.