Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Mie University Research Center for Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Int J Mol Sci. 2021 May 29;22(11):5828. doi: 10.3390/ijms22115828.
Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.
纤连蛋白-C(TNC)是一种大型细胞外基质(ECM)糖蛋白,也是细胞基质蛋白家族的原始成员。TNC 在胚胎发育过程中短暂表达于心脏,但在正常成人中很少检测到;然而,其表达在炎症时强烈上调。尽管 TNC 敲除或过表达的小鼠均未表现出明显的表型,但使用基因工程小鼠结合体外实验的疾病模型揭示了 TNC 在对损伤和心肌修复的反应中的多种重要作用,特别是在炎症的调节方面。在大多数情况下,TNC 通过加重炎症/纤维化似乎使不良的心室重构恶化。此外,越来越多的临床证据表明,高 TNC 水平预示着各种心脏病患者不良的心室重构和预后不良。由于炎症的重要性在心脏病的病理生理学中引起了关注,因此本综述将重点关注 TNC 在各种类型的炎症反应中的作用,如心肌梗死、高血压纤维化、病毒感染或自身免疫引起的心肌炎和扩张型心肌病。还将从临床角度讨论 TNC 作为心肌疾病状况分层和选择适当治疗方法的生物标志物的效用。