Tenascin‐C in Development and Disease of Blood Vessels

Abstract

Tenascin-C (TNC) is an extracellular glycoprotein categorized as a matricellular protein. It is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion, and has a wide range of effects on cell response in tissue morphogenesis and remodeling including the cardiovascular system. In the heart, TNC is sparsely detected in normal adults but transiently expressed at restricted sites during embryonic development and in response to injury, playing an important role in myocardial remodeling. Although TNC in the vascular system appears more complex than in the heart, the expression of TNC in normal adult blood vessels is generally low. During embryonic development, vascular smooth muscle cells highly express TNC on maturation of the vascular wall, which is controlled in a way that depends on the embryonic site of cell origin. Strong expression of TNC is also linked with several pathological conditions such as cerebral vasospasm, intimal hyperplasia, pulmonary artery hypertension, and aortic aneurysm/ dissection. TNC synthesized by smooth muscle cells in response to developmental and environmental cues regulates cell responses such as proliferation, migration, differentiation, and survival in an autocrine/ paracrine fashion and in a context-dependent manner. Thus, TNC can be a key molecule in controlling cellular activity in adaptation during normal vascular development as well as tissue remodeling in pathological conditions. Anat Rec, 297:1747Rec, 297: -1757Rec, 297: , 2014. V C 2014 Wiley Periodicals, Inc.Key words: muscle; tenascin-C; blood vessel Abbreviations used: ECM 5 extracellular matrix; TNC 5 tenascin-C; VSMC 5 vascular smooth muscle cell; aSMA 5 a-smooth muscle actin; SAH 5 subarachnoid hemorrhage.

Serum Tenascin-C as a Novel Predictor for Risk of Coronary Artery Lesion and Resistance to Intravenous Immunoglobulin in Kawasaki Disease – A Multicenter Retrospective Study –

“…17,38, 39 Recently, elevated serum levels of TN-C were reported to reflect local expression and are used as biomarkers for disease activity in pediatric patients with various inflammatory diseases, 40-42 as well as in adults. 15, 16 In this study, we found that the serum TN-C levels of KD patients were elevated in the acute stage and the levels correlated with known inflammatory markers, such as percentage of neutrophils and CRP level, although the correlation coefficients were not high. In a mouse KD model, vascular with platelet count (P=0.023); however, the correlation coefficients were not high ( Table 1).…”

“…Analyses of several disease models have shown that the major sources of TN-C in vascular disease are medial smooth muscle cells and fibroblasts, especially myofibroblasts. 15, 16 Various proinflammatory cytokines and growth factors, in addition to mechanical stress, upregulate TN-C expression. Transforming growth factor-β, one of the key modulators of KD arteritis, 44 is also known to induce TN-C expression.…”

“…[15][16][17] It has diverse functions in the regulation of cell behavior and tissue remodeling in many developmental and pathological processes. 18-20 A growing number of studies have reported that serum TN-C is elevated in various cardiovascular diseases and can be used as a biomarker for the diagnosis of disease activity, as well as a predictor of outcome in patients with aortic aneurysm/dissection, 21,22 MI, 23 and dilated cardiomyopathy.…”

Extracellular Matrix Remodeling in Vascular Development and Disease

“…The major source is medial smooth muscle cells [11]. However, TNC in the vascular system appears more complex in contrast to the heart [7].…”

“…Although the grossly normal phenotype of knockout mice suggests the importance of redundancy and compensatory mechanisms during embryonic development, it is not straightforward to understand its molecular function. Meanwhile, TNC expression is linked to a range of vascular diseases, such as aortic aneurysm, acute aortic dissection, and Kawasaki disease (reviewed in [11,17], also see Yoshikane et al in this proceeding). Increasing numbers of studies have reported that TNC is highly upregulated, associated with inflammation and destruction of the vascular wall, suggesting that TNC may be a diagnostic biomarker.…”