Possible Roles of the Tenascin Family During Heart Development and Myocardial Tissue Remodeling

Abstract

The tenascins are a family of extracellular matrix proteins. Tenascin-C (TNC) is expressed during embryogenesis or cancer invasion. Tenascin-X (TNX) is ubiquitously expressed, with the highest levels in the heart. To clarify the role of TNC and TNX in the heart, we analyzed TNC and TNX expression patterns in embryonic hearts of mice by immunohistochemistry and in situ hybridization. TNC was transiendy expressed at four important steps of early heart development: (1) differentiation of cardiomyocytes from the mesoderm, (2) formation of endocardial cushion tissue, (3) development of the outflow tract, and (4) migration of the proepicardial cells (precursors of coronary vessels). After the expression of TNC was downregulated, TNX was expressed by epicardial cells invading the myocardial layer and forming vascular channels. In normal adult hearts, TNC was sparse but reappeared under pathological conditions. During tissue repair after electric injury to the ventricle of mice, TNC appeared at the border zone between intact and injured myocardium, the most active sites of tissue remodeling during the acute stage. These expression patterns strongly suggest the important roles of TNC in tissue remodeling of the myocardium as well as during early heart development. However, in TNC knockout mice, the heart developed normally, and the myocardial tissue repair seemed to proceed normally. Furthermore, our findings did not show that TNX compensates for the loss of TNC.