Tenascin-C in cardiac disease: a sophisticated controller of inflammation, repair, and fibrosis

Abstract

Tenascin-C (TNC) is a large extracellular matrix glycoprotein classified as a matricellular protein that is generally upregulated at high levels during physiological and pathological tissue remodeling and is involved in important biological signaling pathways. In the heart, TNC is transiently expressed at several important steps during embryonic development and is sparsely detected in normal adult heart but is re-expressed in a spatiotemporally restricted manner under pathological conditions associated with inflammation, such as myocardial infarction, hypertensive cardiac fibrosis, myocarditis, dilated cardiomyopathy, and Kawasaki disease. Despite its characteristic and spatiotemporally restricted expression, TNC knockout mice develop a grossly normal phenotype. However, various disease models using TNC null mice combined with in vitro experiments have revealed many important functions for TNC and multiple molecular cascades that control cellular responses in inflammation, tissue repair, and even myocardial regeneration. TNC has context-dependent diverse functions and, thus, may exert both harmful and beneficial effects in damaged hearts. However, TNC appears to deteriorate adverse ventricular remodeling by proinflammatory and profibrotic effects in most cases. Its specific expression also makes TNC a feasible diagnostic biomarker and target for molecular imaging to assess inflammation in the heart. Several preclinical studies have shown the utility of TNC as a biomarker for assessing the prognosis of patients and selecting appropriate therapy, particularly for inflammatory heart diseases.