Tenascin-C (TNC) is a large extracellular matrix glycoprotein classified as a matricellular protein that is generally up-regulated at high levels during physiological and pathological tissue remodelingand 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-expressedin 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 vitroexperiments 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 functionsand, 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.

中文翻译：

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心脏疾病中的Tenascin-C：炎症，修复和纤维化的复杂控制者。

Tenascin-C（TNC）是一种大的细胞外基质糖蛋白，被归类为基质细胞蛋白，通常在生理和病理组织重塑过程中被上调，并参与重要的生物信号传导途径。在心脏中，TNC在多个细胞中瞬时表达胚胎发育过程中的重要步骤，在正常的成年心脏中很少检测到，但在与炎症相关的病理条件下（如心肌梗塞，高血压性心肌纤维化，心肌炎，扩张型心肌病和川崎病）以时空受限的方式重新表达。尽管其特征和时空限制表达，TNC基因敲除小鼠发展出大致正常的表型。然而，使用TNC无效小鼠的各种疾病模型与体外实验相结合，揭示了TNC和控制炎症，组织修复乃至心肌再生中细胞反应的多个分子级联反应的许多重要功能。TNC具有上下文相关的多种功能，因此可能在受损的心脏中发挥有害和有益的作用。然而，在大多数情况下，TNC似乎通过促炎和纤维化作用使不良的心室重塑恶化。它的特异性表达也使TNC成为可行的诊断生物标志物和分子影像学评估心脏炎症的靶标。几项临床前研究表明，TNC作为一种生物标志物可用于评估患者的预后并选择适当的治疗方法，特别是对于炎症性心脏病。